Parvovirus B19 is a nonenveloped virus with single-stranded DNA that has a tropism for erythroid progenitor cells. The virus replicates within these cells and is cytotoxic, resulting in a pure red cell aplasia. It is a common viral disorder that is transmitted via droplets, transplacentally, and through blood transfusions. It is acquired early in life and is so common that greater than 90% of the elderly are seropositive. In general, a normal host clears the infection and at most develops a transient clinically insignificant anemia. This infection, however, becomes hematologically significant in patients with chronic hemolytic anemias, such as sickle cell, thalassemia, and congenital spherocytosis; in patients with acute malaria; and in patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS).