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Mitch, Frank and Beanie are disillusioned with their personal lives begining when Mitch’s nymphomanic girlfriend, Heidi, cheats on him, then former party animal Frank gets married, but unwilling to get go of his wild life, and Beanie is a family man seeking to reclaim his wild and crazy youth. Beanie suggests that they form their own fraternity in Mitch’s new house on a college campus to re-live their glory days by bringing together a variety of misfit college students, losers, middle-aged and elderly retirees as their new friends and later try to avoid being evicted by the new Dean of Students, Pritchard, whom still holds a personal grudge against all three of them.

In Chicago, the former photographer and presently advertising executive Mathew (Josh Hartnett) is closing a business deal in a fancy restaurant with a Chinese representative, when he sees a woman that looks like his former passion Lisa (Diane Kruger). Two years ago, Lisa and Matthew had a love affair, and Lisa simply vanished when Matthew invited her to move with him to New York, where he had the invitation for a better job, and Matthew is still obsessed for her. Matthew decides to follow Lisa, and when he meets her, he realizes that Lisa is indeed another woman (Rose Byrne) with the same name. Matthew stays in Chicago with his friend Luke (Matthew Lillard) and decides to investigate the mystery.