The story follows two friends and roommates. The Gujarati rebel Jignesh "Jerry" Patel (Akshay Kumar) and clean simpleton Nick Mathur (John Abraham), who live in London. Jerry does odd jobs for a living as he is an undergraduate but Nick has a white-collar job. However, both find themselves jobless due to the economic downturn. Jerry has a school-age nephew named Veer (Master Virej Desai) whom he looks after, as the child has lost his parents. Nick is to marry his girlfriend, Radhika Awasthi (Deepika Padukone), who dreams of a lovely wedding, a great honeymoon and a wonderful house to live in after marriage.
Out of a job, Jerry finds it difficult to even pay the school fees of his nephew because of which the government is on the verge of giving the custody of his nephew to a foster family. Nick fears he won’t be able to fulfill the dreams of his to-be wife. It is to tide over the difficult times that Jerry and Nick turn to the oldest profession in the world. Jerry and Nick become male escorts for the company "Desi Boyz", fulfilling the fantasies of girls and ladies. Jerry is unable to prevent his nephew from being sent to a foster home; and Nick loses Radhika when she learns of what he has been up to while she is away in India. Frustrated, Nick blames Jerry for forcing him into the profession and asks him to move out of his house and life.
Nick now tries hard to win Radhika back and help comes from the most unlikely source – Radhika’s father Suresh (Anupam Kher) who has come to London with her. Meanwhile, Jerry registers in college again to complete his graduation so that he can earn enough money to get his nephew back home. In college, Jerry meets Tanya Sharma (Chitrangada Singh) who used to be his over-sized classmate and is now an attractive professor at the same college. Sparks fly between Jerry and Tanya. To make Nick jealous, Radhika dates a man named Ajay (Omi Vaidya). Nick starts to pick on Ajay, often calling him Vijay intentionally. After some reconsideration, Radhika forgives Nick, but Nick rejects her after she disapproves of Jerry. Meanwhile, Jerry graduates college and also wins Tanya's heart. Nick comes and apologizes to Jerry. All is forgiven when Nick and Jerry reconcile. Jerry then helps Radhika win back Nick.
Nick then helps Jerry get a decent high paying job, and Jerry decides to go to court and get back the custody of his nephew. Ajay turns out to be the lawyer against Jerry's case. He decides to get revenge on Nick by not letting Jerry win his case. Ajay tells the court about Jerry being a male escort and what a bad role model he would be to his nephew, bringing in 3 witnesses to testify against Jerry. He asks each of them if they had paid Jerry for sex; but only one says yes. Ajay is on the verge of winning, but Mr Desi Boyz comes into the courtroom and influences the judge. Then, Jerry makes an inspiring speech to the judge. The case is in his favour and he ends up winning and gaining full custody of Veer. The recession ends and everyone is happy. In a short ending scene, a newspaper article is shown, that states the recession will strike back, then Mr. Desi Boyz gives a call and says that he has gotten the licence for a branch in Mumbai.