Glycoprotein IIb/IIIa receptor antagonists (GPRAs) are widely used in the management of a variety of patients with acute coronary syndromes. Major adverse reactions to these agents include bleeding and thrombocytopenia. Immune mechanisms responsible for severe thrombocytopenia seen with GPRAs have been hypothesized for all 3 agents currently available in the United States, although specific laboratory tests are not available for use in routine practice. A review of published research for GPRA-induced thrombocytopenia (GIT) is provided. Although the incidence of severe GIT is relatively low, the implications for patients are potentially life threatening. Prompt recognition of severe thrombocytopenia is essential to facilitate the necessary care of patients. Treatment strategies include the modification of drug regimens and other interventions targeting the reduction of immediate bleeding risk and the provision of supportive care measures. A review of published research supporting the conservative use of corticosteroids and intravenous gamma globulin in this syndrome is provided. Clinicians identifying severe thrombocytopenia after GPRA exposure are encouraged to report these events, following national and institutional guidelines.