Permadeath

You can only die once
This is specifically a rule that only applies to players. A player that dies once is gone for good. There will be no player resurrection in this game, not even through wishes.

But, no death effects
Players and most enemies will not be allowed to use instant-death effects, or save-or-die spells.

In case of a party wipe
When the party faces a huge set back, so that most or all of the players have died. Then the DM has three options. He can either say that this is a bittersweet end of the campaign; That the campaign continues, using the deaths of the party as the basis for a new story; or that he will "load a save file", essentially undoing all events up to a certain point, and giving the players another shot at the encounter.

As a player, it is important to understand that the DM has these three options, but that it is ultimately his choice on how he wishes to continue the story (or not).