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I was slightly surprised to see that, in addition to the above excellent answer by KRyanthe above excellent answer by KRyan, there is no actual attempt at listing the mechanical differences. So I'll indicate a few. It's also quite an interesting exercise to look at D&D in this way, since 5e is generally considered to have evolved from 3e, not 4e; but naturally players who entered when 4e was current would not be aware of that.

  • The biggest change is that the at-will / encounter / daily powers system is gone. Instead, powers or other special effects are limited by the number of times they can be used per long or short rest (which may be more than one). A "short" rest in 5e is 1 hour long - not the 5 minutes it was in 4e - so this does not correspond to an encounter-based limit.
  • Likewise, the allocation of powers between classes is very different. Different classes get different sets of powers at different times, usable at different frequencies. In particular, martial and fighting classes get fewer and less powerful abilities, but typically have the ability to use them more often, or have no limits on their usage frequency at all. This was partly due to a common complaint with 4e, that Fighter powers like Come And Get It were difficult to visualize, since it was not clear how a mundane fighter wielding a sword would be able to cause enemies to unwillingly move towards them.
  • Magic using classes have the greatest variety of powers. Instead of at-will/encounter, they're limited by spell slots, which give casters a certain number of times per day (or per long rest) that they can use each level of spell. Unlike 3e and 4e, they are not limited in the number of times a specific spell can be used, only the total number of usages of spells of particular levels.
  • AC is now the only "defense". Any ability which would have targeted Fortitude, Reflex, or Will in 4e now instead gives a saving throw; rather than the attacker rolling and trying to beat the target's defense, the target rolls against a difficulty number set by the attacker's ability, and avoid or reduce the attack on a success. There is a saving throw associated individually with each ability score, rather than the "best of two" for each in 4e.
  • The level modifier is also gone. It's replaced by a proficiency bonus, which increases much more slowly (from +2 to +6 over the course of 20 levels) and which is applies only to rolls with which a character is skilled. This is one of the key points in 5e which makes characters substantially more vulnerable, even at high levels.
  • There are only 20 levels. There are no paragon paths and no epic destinies. There is multiclassing, but rather than being feat-based, it allows actual levels to be taken from multiple classes, but does have more restrictions based on ability score results. There is, however, a background which is chosen independently of your class at level 1, which gives proficiency in two skills and a standard non-combat ability.

I was slightly surprised to see that, in addition to the above excellent answer by KRyan, there is no actual attempt at listing the mechanical differences. So I'll indicate a few. It's also quite an interesting exercise to look at D&D in this way, since 5e is generally considered to have evolved from 3e, not 4e; but naturally players who entered when 4e was current would not be aware of that.

  • The biggest change is that the at-will / encounter / daily powers system is gone. Instead, powers or other special effects are limited by the number of times they can be used per long or short rest (which may be more than one). A "short" rest in 5e is 1 hour long - not the 5 minutes it was in 4e - so this does not correspond to an encounter-based limit.
  • Likewise, the allocation of powers between classes is very different. Different classes get different sets of powers at different times, usable at different frequencies. In particular, martial and fighting classes get fewer and less powerful abilities, but typically have the ability to use them more often, or have no limits on their usage frequency at all. This was partly due to a common complaint with 4e, that Fighter powers like Come And Get It were difficult to visualize, since it was not clear how a mundane fighter wielding a sword would be able to cause enemies to unwillingly move towards them.
  • Magic using classes have the greatest variety of powers. Instead of at-will/encounter, they're limited by spell slots, which give casters a certain number of times per day (or per long rest) that they can use each level of spell. Unlike 3e and 4e, they are not limited in the number of times a specific spell can be used, only the total number of usages of spells of particular levels.
  • AC is now the only "defense". Any ability which would have targeted Fortitude, Reflex, or Will in 4e now instead gives a saving throw; rather than the attacker rolling and trying to beat the target's defense, the target rolls against a difficulty number set by the attacker's ability, and avoid or reduce the attack on a success. There is a saving throw associated individually with each ability score, rather than the "best of two" for each in 4e.
  • The level modifier is also gone. It's replaced by a proficiency bonus, which increases much more slowly (from +2 to +6 over the course of 20 levels) and which is applies only to rolls with which a character is skilled. This is one of the key points in 5e which makes characters substantially more vulnerable, even at high levels.
  • There are only 20 levels. There are no paragon paths and no epic destinies. There is multiclassing, but rather than being feat-based, it allows actual levels to be taken from multiple classes, but does have more restrictions based on ability score results. There is, however, a background which is chosen independently of your class at level 1, which gives proficiency in two skills and a standard non-combat ability.

I was slightly surprised to see that, in addition to the above excellent answer by KRyan, there is no actual attempt at listing the mechanical differences. So I'll indicate a few. It's also quite an interesting exercise to look at D&D in this way, since 5e is generally considered to have evolved from 3e, not 4e; but naturally players who entered when 4e was current would not be aware of that.

  • The biggest change is that the at-will / encounter / daily powers system is gone. Instead, powers or other special effects are limited by the number of times they can be used per long or short rest (which may be more than one). A "short" rest in 5e is 1 hour long - not the 5 minutes it was in 4e - so this does not correspond to an encounter-based limit.
  • Likewise, the allocation of powers between classes is very different. Different classes get different sets of powers at different times, usable at different frequencies. In particular, martial and fighting classes get fewer and less powerful abilities, but typically have the ability to use them more often, or have no limits on their usage frequency at all. This was partly due to a common complaint with 4e, that Fighter powers like Come And Get It were difficult to visualize, since it was not clear how a mundane fighter wielding a sword would be able to cause enemies to unwillingly move towards them.
  • Magic using classes have the greatest variety of powers. Instead of at-will/encounter, they're limited by spell slots, which give casters a certain number of times per day (or per long rest) that they can use each level of spell. Unlike 3e and 4e, they are not limited in the number of times a specific spell can be used, only the total number of usages of spells of particular levels.
  • AC is now the only "defense". Any ability which would have targeted Fortitude, Reflex, or Will in 4e now instead gives a saving throw; rather than the attacker rolling and trying to beat the target's defense, the target rolls against a difficulty number set by the attacker's ability, and avoid or reduce the attack on a success. There is a saving throw associated individually with each ability score, rather than the "best of two" for each in 4e.
  • The level modifier is also gone. It's replaced by a proficiency bonus, which increases much more slowly (from +2 to +6 over the course of 20 levels) and which is applies only to rolls with which a character is skilled. This is one of the key points in 5e which makes characters substantially more vulnerable, even at high levels.
  • There are only 20 levels. There are no paragon paths and no epic destinies. There is multiclassing, but rather than being feat-based, it allows actual levels to be taken from multiple classes, but does have more restrictions based on ability score results. There is, however, a background which is chosen independently of your class at level 1, which gives proficiency in two skills and a standard non-combat ability.
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I was slightly surprised to see that, in addition to the above excellent answer by KRyan, there is no actual attempt at listing the mechanical differences. So I'll indicate a few. It's also quite an interesting exercise to look at D&D in this way, since 5e is generally considered to have evolved from 3e, not 4e; but naturally players who entered when 4e was current would not be aware of that.

  • The biggest change is that the at-will / encounter / daily powers system is gone. Instead, powers or other special effects are limited by the number of times they can be used per long or short rest (which may be more than one). A "short" rest in 5e is 1 hour long - not the 5 minutes it was in 4e - so this does not correspond to an encounter-based limit.
  • Likewise, the allocation of powers between classes is very different. Different classes get different sets of powers at different times, usable at different frequencies. In particular, martial and fighting classes get fewer and less powerful abilities, but typically have the ability to use them more often, or have no limits on their usage frequency at all. This was partly due to a common complaint with 4e, that Fighter powers like Come And Get It were difficult to visualize, since it was not clear how a mundane fighter wielding a sword would be able to cause enemies to unwillingly move towards them.
  • Magic using classes have the greatest variety of powers. Instead of at-will/encounter, they're limited by spell slots, which give casters a certain number of times per day (or per long rest) that they can use each level of spell. Unlike 3e and 4e, they are not limited in the number of times a specific spell can be used, only the total number of usages of spells of particular levels.
  • AC is now the only "defense". Any ability which would have targeted Fortitude, Reflex, or Will in 4e now instead gives a saving throw; rather than the attacker rolling and trying to beat the target's defense, the target rolls against a difficulty number set by the attacker's ability, and avoid or reduce the attack on a success. There is a saving throw associated individually with each ability score, rather than the "best of two" for each in 4e.
  • The level modifier is also gone. It's replaced by a proficiency bonus, which increases much more slowly (from +2 to +6 over the course of 20 levels) and which is applies only to rolls with which a character is skilled. This is one of the key points in 5e which makes characters substantially more vulnerable, even at high levels.
  • There are only 20 levels. There are no paragon paths and no epic destinies. There is multiclassing, but rather than being feat-based, it allows actual levels to be taken from multiple classes, but does have more restrictions based on ability score results. There is, however, a background which is chosen independently of your class at level 1, which gives proficiency in two skills and a standard non-combat ability.