The risk of developing cancer after solid organ transplantation (SOT) is about 5- to 10-fold greater than that of the general population. The cumulative risk of cancer rises to more than 50% at 20 years after transplant and increases with age, and so children receiving transplants are at high risk of developing a malignancy. Posttransplant lymphoproliferative disease (PTLD) is the most common cancer observed in children following SOT, accounting for half of all such malignancies. PTLD is a heterogeneous group of disorders with a wide spectrum of pathologic and clinical manifestations and is a major contributor to long-term morbidity and mortality in this population. Among children, most cases are associated with Epstein-Barr virus infection. This article reviews the pathology, immunobiology, epidemiology, and clinical aspects of PTLD, underscoring the need for ongoing systematic study of complex biologic and therapeutic questions.