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What is your party's level and composition?
There are also ghosts.
Rejuvenation (Su): In most cases, it’s difficult to destroy a ghost through simple combat: the “destroyed” spirit restores itself in 2d4 days. Even the most powerful spells are usually only temporary solutions. The only way to permanently destroy a ghost is to determine the reason for its existence and set right whatever prevents it from resting in peace. The exact means varies with each spirit and may require a good deal of research, and should be created specifically for each different ghost by the GM.
As a GM, you can also give this ability to any creature (making up a story how it obtained it), creating a creature that is no harder to defeat than a normal one, but difficult to get rid off permanently.
You can also give a creature a regeneration that can only be stopped by some specific action. See for example the story of Anteus who couldn't be defeated as long as he was touching the ground.
Be wary of forcing PCs to resort to out-of-character solutions in order to defeat the big bad (BBEG). Part of the fun of making it to high levels in a campaign is getting to use those powers and abilities. Nothing wrong with making PCs solve problems and look for clues on ways to defeat the villain (maybe they have to find the ancient weapons or relics that will allow them to bypass the impossible damage reduction or regeneration), but let them use their abilities to defeat the enemy. Good luck!