Barry Scheck looked and sounded different that the other members of the defense team with his ill-fitting suits, bushy hair, and a New York accent. A Clinical Law Professor at the Benjamin N. Cardozo School of Law, Scheck both taught and defended criminal cases. Scheck's causes seemed mostly honorable. Realizing that DNA testing could free convicted prisoners, Scheck and his Partner Peter Neufeld created the "Innocence Project", which helped fifteen inmates go free within a few years.

Scheck had initially been hired to evaluate and brief Shapiro on the admissibility of DNA evidence. With the increasing importance of DNA evidence, Scheck's involvement in Simpson's defense rose in siginificance throughout the trial. Some legal experts regarded Scheck's eight-day cross examination of LAPD criminologist Dennis Fung as "the greatest cross examination since the Scopes trial," with Scheck's frequent question, "where is it, Mr. Fung?" "To Scheck" entered the legal vocabulary and came to mean to bully a witness, or to act self-righteous or melodramatic.

Scheck delivered part of the closing arguments, arguing that the evidence against Simpson had been planted or contaminated by the LAPD.

Following the trial, Scheck became an advocate for forensic science, speaking across the nation. He serves on the New York State Commission on Forensic Science and lectures to police departments and prosecutors across the country about the proper use of genetic fingerprinting. Scheck assisted Cochran in the Abner Louima case, in which Louima was allegedly sodomized by New York police officers. Scheck also has advised Colorado police investigators on medical evidence in the JonBenet Ramsey case.