Weiss studied at Columbia University,and later graduated from the Yale University School of Medicine in 1970, completing an internship in internal medicine at the New York University Medical Center then returning to Yale for a two-year residency in psychiatry. He went on to become Head of Psychiatry, Mount Sinai Medical Center, Miami.
According to Weiss, in 1980 one of his patients, "Catherine", began discussing past-life experiences under hypnosis. Weiss did not believe in reincarnation at the time but, after confirming elements of Catherine's stories through public records, came to be convinced of the survival of an element of the human personality after death. Weiss claims he has regressed more than 4,000 patients since 1980.
Weiss advocates hypnotic regression as therapy, claiming that many phobias and ailments are rooted in past-life experiences whose acknowledgment by the patient can have a curative effect. Weiss also writes about messages received from the Ascended masters he claims to have communicated with through his subjects. Weiss has explained such apparent discrepancies as the work of what he terms the superconscious mind, a state of hyperconscious awareness.