A chance meeting between Ayan (Ranbir Kapoor) and Alizeh (Anushka Sharma) ends up with both kissing instinctively. Later, when both break up with their respective lovers, Lisa (Lisa Haydon) and Dr. Faisal Khan (Imran Abbas), the two begin to spend time together at discos, restaurants and tourist places. While Ayan falls in love with Alizeh, she considers him to be a friend. One day, Alizeh stumbles upon Ali (Fawad Khan), her ex-boyfriend, who wants to reconcile with her. Confused, Alizeh stops hanging out with Ayan and the two cease communication. A few days later, Alizeh calls and invites Ayan to her wedding with Ali in Lucknow. Ayan is petrified on hearing this but agrees to the invitation. At the wedding, he tells Alizeh he loves her but she rejects his feelings causing Ayan to leave the ceremony heartbroken.
At the airport to board a flight to Frankfurt, Ayan meets Saba (Aishwarya Rai), a poetess, who is leaving for Vienna. She consoles Ayan and gives him a note with her poetry and number on it. Ayan calls her after 3 months stating that he is in Vienna and wants to meet her. Saba meets him at a disco and later, they have sex. Ayan learns that Saba is divorced and has no place for love in her heart. Ayan also meets Saba’s ex husband Tahir Taliyar Khan (Shah Rukh Khan) in a gallery, who tells him that love is not a weakness but empowering. Ayan who had blocked Alizeh from everywhere, finally calls and reconnects with her. Ayan begins to send pictures of Saba to Alizeh to induce jealousy. One day Alizeh informs Ayan that she’s coming to Vienna and wants to meet him. Ayan invites her for dinner, but Alizeh thinks Ayan has finally found love in Saba and is happy for him. Meanwhile Saba begins to develop feelings for Ayan but he still loves Alizeh.
Ayan continues to harbour love for Alizeh and becomes a famous singer. He meets Ali one day and realises that Alizeh and he have parted ways. Ayan goes to Alizeh’s favourite point and waits there until she arrives. Alizeh tells Ayan that she is diagnosed with Stage 4 Cancer and will not live much longer. Ayan and Alizeh try to make the best of their last few moments together. Ayan tries to make Alizeh love him but Alizeh is stubborn. This leads to a fight between the two, and Alizeh decides to leave him. Eventually, Ayan makes peace with the fact that he and Alizeh can at best be friends and nothing more. The screen blacks out and goes back to the beginning where Ayan, still a popular singer is giving a interview based on the love of his life (Alizeh, who has already died). Ayan sings The song “Channa Mereya” which is inspired by Alizeh, then finishes the interview.