Tilda Swinton was in charge of designing how her character looked and talked. She was very keen to take the part as it was completely different from anything else she had ever done before.
Norman Lloyd, who plays a supporting role in this movie, was 100 years old during filming. Lloyd (who was born in November 1914) had his first role in a Broadway show in 1927 and his first movie role in 1939; his career has included roles for Alfred Hitchcock, Orson Welles, Charles Chaplin, and Martin Scorsese. After being blacklisted during the Red Scare of the 1950s, Alfred Hitchcock again employed him--this time as a producer, on the TV series Alfred Hitchcock Presents (1955), and then he enjoyed an acting resurgence during the 1980s after being cast as Dr. Daniel Auschlander on St. Elsewhere (1982). Lloyd claimed that most of his lines were improvised, and that it was the first time in his career that he improvised during a performance.
Norman Lloyd met Judd Apatow over lunch to discuss his part in the film. Lloyd claimed that Apatow was surprised that Lloyd, then 99, had driven himself to the appointment and offered to walk with him two blocks back to his car. Lloyd surmised that the walk back to his car was part of the job interview, confirming to Apatow that he was ambulatory. Apatow later expressed his amazement at Lloyd's independence, observing that he flew to New York and arrived on set alone, never asked for special services, and never needed to take breaks during filming.
Colin Quinn, who plays Amy Schumer's father, spent a lot of time with her real dad who really does have multiple sclerosis.
Chris Rock was on the set when LeBron James's scenes were filmed and he came up with several of the lines that James says in the film.