According to Production Weekly, the reason the trio are getting together for a third go-around is to bring Admiral Stansfield Turner's novel-with-the-exceptionally-long-name Burn Before Reading: President, CIA Directors and Secret Intelligence to the screen. Man, that is long. Anyway, in the novel, a CIA agent is writing a tell-all book about his life in the agency and then loses the disk he saved the book on. The disk then passes through the hands of various people who all end up dead because they've seen what's on the disk.
Although he's played a CIA agent before, in Confessions of a Dangerous Mind and in the recent Syriana, Clooney will not be returning to that role again in this film. Instead, he will go a different route and play the assassin who kills anyone who has come in contact with the disk. I can't recall a film where Clooney played this kind of part so this will be a definite departure for an actor who normally prefers the "morally ambiguous but basically a good guy" roles in film such as Ocean's Eleven, Three Kings or Out of Sight.
No word yet on other casting but I'll bet Coen alums Francis McDormand and John Goodman will probably show up somewhere. At least I hope they do. Production on Burn Before Reading (my new preferred shorter title for the film) is scheduled to begin in August of next year after Clooney wraps his current project Leatherheads, a comedy set in the world of 1920's football, in which he both starts and directs. Busy man, huh?