Karan Kapoor (Saif Ali Khan) works with one of India's leading newspapers as a cartoonist. Hum Tum are his cartoon characters. Hum Tum because that's how he sees the world divided. No countries, no religions, just two divisions - boys and girls. Karan met Rhea (Rani Mukerjee) for the first time in Amsterdam. They disagreed on everything. So to put things right, Karan innocently kissed her... to confirm their friendship. But things went worse with the unstable Rhea and the meeting ended on a bad note. It's been 10 years since their first encounter and they meet again and become friends despite their differences. Rhea has gone through some personal tragedies in her life, lots of ups and downs but Karan has always been there for her. During this time, she has moved all over the place, from Mumbai to Paris to New York and back to Mumbai. But despite their mishaps, destiny has bigger plans for Karan and Rhea.