The ability of platelets to aggregate and to form a platelet plug is central to the maintenance of normal hemostasis. When platelets have normal function, the severity of bleeding is related to the degree of thrombocytopenia. In patients with normal platelet production, the most common cause of thrombocytopenia is due to immune mechanisms that results in platelet injury and removal from the circulation. These mechanisms involve the binding of platelet-associated immunoglobulins and are classified as immune. Immune thrombocytopenias can be caused by autoantibodies (autoimmune thrombocytopenia), alloantibodies (isoimmune thrombocytopenia), or drug-induced immune complexes and conditions secondary to autoimmune disorders such as systemic lupus erythematosus. In this paper the focus is on alloimmune thrombocytopenias resulting from the formation of alloantibodies to platelet specific antigens. The clinical importance of the platelet alloantigens is due to their ability to elicit alloantibody production. Alloantigens, also referred to as isoantigens, are substances that induce the production of alloantibodies when they are infused into individuals of the same species who lack the specific alloantigen.