The role of Harry Goldfarb was originally intended for Giovanni Ribisi. Director Darren Aronofsky wanted Ribisi for the role because he resembled the look of Harry Goldfarb, who had curly blonde hair in Hubert Selby Jr's 1978 Novel.
During Ellen Burstyn's impassioned monologue about how it feels to be old, cinematographer Matthew Libatique accidentally let the camera drift off-target. When director Darren Aronofsky called "cut" and confronted him about it, he realized the reason Libatique had let the camera drift was because he had been crying during the take and fogged up the camera's eyepiece. This was the take used in the final print.
In addition to having a camera mounted to her for certain sequences, Ellen Burstyn, spent four hours every morning being fitted with prosthetics, wearing four different necks (both fat and emaciated), two different fat suits (a 40-pound and 20-pound suit), and nine different wigs.
The Tappy Tibbons material was shot in one day, with Christopher McDonald improvising a good deal of his material. At the end, the SAG extras for the audience and the crew all gave him a standing ovation.
The man peeling the orange (and the orange truck) in the scene where the characters go to receive a new shipment of drugs not only indicates their next destination - Florida - but also serves as a nod to the Godfather films, where the presence of oranges indicated disaster.
During one scene in which Ellen Burstyn is hallucinating, her entire apartment is taken apart piece by piece as though it was the set of a television show. Several crewmembers of the mock television show pass Burstyn in her chair, including a man carrying a clip board with the Greek letter/mathematical symbol "Pi" on the back - Darren Aronofsky's first film.
In the opening scene you can hear the sounds of a string quartet tuning up for a performance in the soundtrack. Just before the title rolls down, you hear a conductor tap on his music stand to ready the quartet for a performance. The people tuning up are "The Kronos Quartet", who played most of the music for the film. The maestro bringing them to attention is Darren Aronofsky, the director.
The overhead shot of Marion in the bathtub followed by her screaming underwater was an exact replica of a shot in the Japanese animated thriller, Perfect Blue. Darren Aronofsky bought the remake rights to the film just to use that one sequence.
In the scene that Marion calls Big Tim, there is a shot of his phone number on a piece of paper. It was not the standard "555-" number used in movies. They were able to get away with this because only six digits of the phone number are visible. However if you listen carefully, Tyrone does speak all seven digits. But, after the scene where Harry is with the doctor, Marion turns over the photograph of her and Harry, revealing the full telephone number.
When Ellen Burstyn first read the script offered by Darren Aronofsky, she was horrified by it and rejected the role. It was not until after she watched a video of Pi Aronofsky's previous film - that she changed her mind and accepted the role.
The pills Sarah Goldfarb takes in the film are actually Synthroid pills taken for thyroid hormone replacement for people with hypothyroidism, this is also true for the pills Marion, Tyrone and Harry take before the party.
The trivia items below may give away important plot points.
Tappy Tibbons's regimen consists of "three things, which is all I did to change my life". #1, "no red meat", and #2, "no refined sugar", are repeated throughout the film. #3 can only be glimpsed by freeze-framing a scene with the whiteboard that Tappy is writing on (it can also be accessed (and you can view the entire third section) on the director's cut DVD, by choosing the Chapter Selections; scroll to 21-24 and press up twice before pressing Enter).