Sometimes people will try to save the Giant Skunk for when they're level 9 to fight it to prevent people from screwing them over too much at the end. However my friends and I have debated about whether or not you can use the Annihilation card to remove the Giant Skunk card from the game after someone plays it.
Giant Skunk: They may not help you, backstab you, or use any cards either for or against you -- except for Wandering Monsters and monster enhancers.
Annihilation: Play this card at any time to permanently remove any one card from the game. It does not go to the discard pile . . . put it back in the box and forget it. The target card must be in play when you use Annihilation on it. If an opponent had just played it, it is canceled and has no effect.
Some people say yes, others say no, and still others say it depends on the timing. Which is it?