Karan (Saif Ali Khan) is a cartoonist and a self-styled ladies' man. His daily comic, named "Hum Tum," explores the battle of stereotypical male/female behavior. On a plane from Delhi to New York, he meets Rhea (Rani Mukerji) who doesn't seem to be interested in him. His feeble attempts at flirting go nowhere, but when they have a stop-over in Amsterdam, she agrees to explore the city with him. Karan quickly learns he has little in common with the feisty but proper Rhea, but he won't give up. He ends their contentious time together with an unwelcome kiss. Outraged, Rhea slaps him, and storms off, but Karan insists they'll meet again. After a few months he spots her in a park in New York, and she makes a scene with his girlfriend (Shenaz Treasurywala), who turns out to be Rhea's friend, which ends in their break-up.

Three years later, Karan is helping his mother plan a wedding that turns out to be Rhea's. Rhea is marrying Sameer (Abhishek Bachchan). They bicker again, but this time, they part on good terms. Years later in Paris, Karan is visiting his father (Rishi Kapoor), when he runs into Rhea. He learns from Rhea's mother (Kirron Kher) that Sameer has died in a car accident, and he sets out to help her reclaim her positive outlook on life. Karan returns to Mumbai, and three months later, Rhea and her mother visit. Sensing that she needs to be with a straight-laced, "boring guy," he conspires with Rhea's mother to fix her up with his shy best friend, Mihir (Jimmy Shergill). But eventually Mihir falls in love with a friend of Karan's, Diana (Isha Koppikar) and they get engaged. On the engagement night Rhea learns from drunk Diana about the conspiracy. Mihir makes Rhea realize hers and Karan's love for each other. That night Rhea and Karan consummate their relationship. Karan deems it a mistake and asks Rhea to marry him as he feels he took advantage of her, and that marriage will rectify the mistake. Rhea becomes upset, as she did not consider their actions a mistake; she realizes she loves him but tells Karan that they should not commit one more mistake by marrying for the wrong reasons. Rhea leaves him since Karan projects his confused feelings as guilt rather than as love for her. Karan realises his mistake, and goes out to find her. One year later, Karan and Rhea reunite again. Karan admits his love for her, and they get married and have a baby girl.

Hum Tum (Hindi: हम तुम, translation: Me and You) is a Bollywood romantic comedy movie, released in India on 28 May 2004, directed by Kunal Kohli and produced by Aditya Chopra and Yash Chopra under the Yash Raj Films banner. The movie stars Saif Ali Khan and Rani Mukerji in the lead roles.

Hum Tum follows the encounters of the two main characters until they, after several years and various meetings, become friends and finally fall in love at the end of the movie. The comic characters Hum and Tum have their own animated sequences in the movie, where they represent the current state of Karan's and Rhea's relationship. The animation for this film was done by Kathaa Animations and the Special Effects by Tata Elxsi. The director Kunal Kohli has stated that the film "is inspired from the genre When Harry Met Sally belongs to."

The film was generally received well by critics, and special praise went to Khan's and Mukerji's performances. It won several Filmfare Awards, including Best Actress (Mukerji), Director (Kohli), and Actor in a Comic Role (Khan). In June 2005, Khan won the National Film Award for Best Actor.