Karan(Saif Ali Khan) meets Rhea(Rani Mukerji) in an aircraft, en route to U.S.A. They disagree on practically everything; they are complete opposites. So, to put things right, Karan innocently kisses her, which offends Rhea no end. The budding friendship ends in a disastrous note. Six months later, the duo meet once again in a park in New York. Rhea hasn't forgotten the kiss, Karan loses his girlfriend(Shenaz Treasurywala) in the process. Rhea and Karan continue to bump into each other at various phases of life and gradually become friends. Rhea goes through some personal tragedies in her life, but Karan stands by her. Karan even tries fixing her up with a friend of his Mihir(Jimmy Shergill) with her mother's(Kiron Kher) permission of course but as with everything else, even this doesn't work out. Instead, Mihir gets engaged to Karan's friend Diana(Isha Koppikar).

 But destiny has other plans for Karan and Rhea.