Pimozide, a diphenylbutylpiperidine neuroleptic which is FDA-approved as a backup treatment for Gilles de la Tourette's syndrome, has been used abroad for many years as a treatment of schizophrenia and has been recently reported to be particularly effective in treating monosymptomatic hypochondriacal psychosis and delusional jealousy. Pimozide may also have a role in the treatment of negative schizophrenic symptoms, pain syndromes, and obsessive compulsive disorder. After reviewing the relevant clinical literature supporting these indications, the authors review preclinical studies that provide points of departure regarding biochemical mechanisms underlying this unique therapeutic profile.