In London, a chance meeting between Ayan Sanger(Ranbir Kapoor) and Alizeh Khan(Anushka Sharma) ends up with them kissing instinctively. They spend the night together knowing about each other and become close.Later, when they break up with their lovers, Lisa D'Souza and Dr Faisal Khan, the two go to Paris to spend a week together. While Ayan falls in love with Alizeh, she considers him to be only a friend. One day, Alizeh stumbles upon DJ Ali(Fawad Khan) her ex-boyfriend, who wants to reconcile. Confused, Alizeh stops hanging out with Ayan and they 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 poet, who is leaving for Vienna. She consoles Ayan and gives him a note with her poetry and number on it. Ayan calls after three months stating that he is in Vienna and wants to meet her. Saba meets him at a disco and they end up sleeping together. 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(Shahrukh Khan) in a gallery, who tells him that one-sided 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 found love in Saba and is happy for him. Meanwhile, Saba begins to develop feelings for Ayan, but he loves Alizeh. Seeing his love for Alizeh, Saba leaves Ayan.

Ayan continues to harbour love for Alizeh and becomes a famous singer. He meets Ali one day and realises that they have parted ways. Ayan goes to Alizeh's favourite point and waits there until she arrives.

Alizeh tells Ayan that she is diagnosed with cancer stage IV and will not live much longer. Ayan and Alizeh try to make the best of their time 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 Ayan. 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 an interview based on the love of his life. Ayan sings the song "Channa Mereya" which is inspired by Alizeh, then finishes the interview.