Prior to filming, the cast members portraying patients studied films of Dr. Oliver Sacks' post-encephalitis patients, and Robert De Niro and Robin Williams spent time with Sacks in the hospital observing him and his patients.
For the movie, Robert De Niro filmed a scene with "Lillian T.", the only surviving patient from Oliver Sacks' book, "Awakenings". She was also said to have been the most outspoken patient in the 1974 Yorkshire Television (UK) documentary about the patients, also called "Awakenings".
Robert De Niro wanted Shelley Winters to play his mother. However, the studio insisted that she read for the part first. Winters refused to do so and when she met the casting director, she reportedly put both her Oscars on his desk and said, "Some people think I can act".