Pure red cell aplasia (PRCA) is an uncommon hematologic disorder characterized by the absence of erythroblasts in otherwise normal bone marrow. It is commonly an autoimmune disorder sometimes associated with a congenital error. It may also be acquired in association with thymomas, hematologic malignancies, human parvovirus B19 infection, drugs, and other disease states. Thirty drugs have been implicated as causative in PRCA, but most literature reports describe only one or two patients. Data evaluating possible mechanisms of drug-induced PRCA are extremely limited, with conflicting results from different investigators. The criteria we used were at least five patients reported, reports from at least three separate investigators, and a minimum of one case of probable causality or better using a published assessment scale. With these criteria, phenytoin, azathioprine, and isoniazid had sufficient evidence of causality. All three are documented causes of PRCA and should be considered in any case of selective erythrocyte aplasia.