Lymphoma is the third most common cancer in children and adolescents. Non-Hodgkin's lymphomas comprise a heterogeneous group of tumors with distinct pathologic and clinical characteristics. Over the past three decades, significant advancements have been made in the molecular characterization of these disorders. With the use of intensive multiagent chemotherapy, non-Hodgkin's lymphomas are now among the most successfully treated cancers in the pediatric population. Future goals of therapy include reduction of treatment duration for early-stage patients and identification of novel targets and therapeutics for advanced-stage patients.