Casting for the lead role went through several process. First it was given to Shah Rukh Khan, but he declined due to his neck injury, then it was offered to Vivek Oberoi. Finally the producers casted Jimmy Sheirgill for the part, but they later interchanged his role with Sanjay Dutt who was cast as the patient 'Zaheer'.
This being Rajkumar Hirani's directorial debut, he wanted everything to be authentic. For the dissection room scenes, he considered shooting in a real dissection room, using real dead bodies. With due respect for everyone's feelings, the scene was shot on a set with a real person doubling up as a cadaver.
Rani Mukerji was very keen on this film and had signed on for the role of Chinky, but she couldn't do the film due to date problems. Then Tabu was brought in, but she soon dropped out. Finally, the role went to Gracy Singh.
The Jadu Ki Jhappi scene between Sanajy Dutt and Sunil Dutt was the most memorable scene of their career's. They both were emotional while shooting it and were crying holding each other and didn't even realize that director Rajkumar Hirani had told cut.
Sajid Khan was the first choice for the role of Circuit before Arshad Warsi got it. Also Vivek Oberoi,Anil Kapoor and Shahrukh Khan were all approached to play Munnabhai which was eventually played by Sanjay Dutt.
Some of the background scores used were already used in earlier Vidhu Vinod Chopra movies like Kareeb and Mission Kashmir. In one such scene where there is an emotional confrontation between Sanjay Dutt and rohini hattangadi (who played his mother), the background music is taken from the song "So Ja Chanda" from Mission Kashmir. Both (the scene and the song) depicted strong emotional bonding between mother and son
The scene where munna is looking at the x-ray ,he speculates that the patient is suffering from lymphocercoma of the intestine. It is a tribute to the Rajesh Khanna's film Anand as in that movie Khanna suffered from the same disease.
The movie pays tribute to the movie Anand in a couple of ways. The paralyzed patient is named Anand Benerjee which is a combination of the names of Khanna's character Anand Sehegal and Amitabh' character Bhaskar Benerjee.
Despite Munna Bhai M.B.B.S was the first movie in the Munna Bhai franchise but in this movie Sanjay Dutt hasn't played the role of Munna Bhai for the first time. Earlier Sanjay Dutt played the role of Munna Bhai in Kroadh (1990) and Hum Kisi Se Kum Nahi (2002) both don't belong to the Munna Bhai Franchise .As of 2018 ,Sanjay Dutt later played the role of Munna Bhai in Lagey Raho Munna Bhai (2006) which also belongs to the Munna Bhai Franchise.
According to the director, One of the toughest scenes from the movie is Carrom Board scene from the hospital. It needed to multiple shots multiple actors, a shot at carom table and merged all to make that scene.
Rajkumar Hirani had shot the film on low budget so he had to make certain changes.Rajkumar Hirani wanted to shoot wedding scene of Sanjay Dutt and Gracy Singh on a wedding set.But the wedding gown for Gracy Singh and new set would lift the budget more .Hence he decided to shoot a still scene on a real location located near the sets.The crew members reached the near by wedding hall and requested the management to allow them to shoot the film after the wedding ended.