Parvovirus B19 (PVB19) infection has a varied spectrum of clinical manifestations, ranging from subclinical infection to skin and joint symptoms to hematologic effects with potential fatality. The most common manifestation of PVB19 infection in children is erythema infectiosum (EI). Also known as fifth disease or slapped cheek syndrome, EI presents as an erythematous exanthem limited to the malar eminences that follows a mild prodromal illness. In healthy children, infection is self-limiting and has an excellent prognosis; however, in high-risk pediatric groups (eg, immunocompromised patients, children with hemolytic anemia or prenatal infection), clinical manifestations are hematologic in nature and typically are more severe. Diagnosis often is made clinically. Serologic testing can be confirmatory. Treatment is aimed at symptomatic relief, and a vaccine currently is under investigation.