Rothstein is a Professor of Law at Georgetown University Law Center, specializing in matters of litigation. As a practicing trial lawyer he has handled a variety of civil and criminal cases, including, tort, contract, commercial, corporate, personal injury, and malpractice cases, for both plaintiffs and defendants. Professor Rothstein has briefed and argued many leading evidence cases, including the principal expert evidence case of Daubert v. Merrill-Dow in the United States Supreme Court.

During the deliberations over the Federal Rules of Evidence, Professor Rothstein was adviser to Congress, helping shape the form of the Rules. He subsequently chaired the American Bar Associations' Committee on Evidence that monitored the practical operation of the Rules in the nation's courts, making recommendations for amendments that were ultimately adopted. His long-running series of articles and national conferences is credited with equipping bench and bar to deal with the Rules, and as Chair of the Association of American Law Schools Evidence Section, he helped do the same for the law teaching community.

Professor Rothstein has been adviser on matters of Evidence to the National Academy of Sciences, the Federal Judicial Center, the National Conference of Commissioners on Uniform State Laws, and several federal government agencies, including the Justice Department. In addition to teaching Evidence and Advanced Evidence at Georgetown, Professor Rothstein is a renowned lecturer and well-known media commentator.