Shia LeBouf, during an interview with the BBC to promote the new Transformers: Revenge of the Fallen, confirmed that a follow-up to Indian Jones and the Kingdom of the Crystall Skull is in the works.

Previously confirmed by George Lucas, Shia said that, "Steven [Spielberg] just said that he cracked the story on it before I left and I think they're gearing that up" during the interview.

In the past, when asked the creator of the franchise had said he was waiting to come up with a story for the potential follow-up.  Sounds like everything is in place now.