In Volume 8 of this series Archer and Harris [7] reviewed the chemistry and pharmacology of narcotic antagonists. Since that time research in this field has increased enormously as evidenced by the fact that in the decade 1962–72 over 500 references to pentazocine have appeared in the literature. It is beyond the scope of this chapter to review the field exhaustively. Instead, we have concentrated our attention on the major developments in the field. In 1965 nalorphine was the only narcotic antagonist available for clinical use which was limited to the treatment of opiate overdosage. Since that time pentazocine has been marketed as a parenteral and oral analgesic and naloxone has been introduced into clinical practice as an opiate antagonist. A number of other narcotic antagonists are undergoing clinical trials as analgesics and cyclazocine [51, 71, 102, 132], naloxone [45, 74, 161] and naltrexone [103, 135] are being investigated as modalities for the treatment of opiate abuse.