Burkitt lymphoma and diffuse large B-cell lymphoma represent the majority of mature B-cell non-Hodgkin lymphomas in children, adolescents, and young adults. Although they are characterized by specific clinical and biological nuances, the 2 diseases share significant clinicopathologic overlap and are treated with the same chemotherapy regimens in pediatrics. Modern-day chemotherapy protocols achieve overall event-free survival rates of nearly 90%. The addition of the anti-CD20 monoclonal antibody rituximab to backbone chemotherapy holds great promise for improving long-term curative outcomes while diminishing acute and long-term toxicities. However, in the contemporary era, the long-term survival for patients with relapsed or refractory disease is meager. The role of hematopoietic stem cell transplantation in children, adolescents, and young adults with relapsed/refractory disease is currently being defined. Meanwhile, novel humoral and cellular immunotherapies, as well as agents targeting specific molecular pathways that drive lymphomagenesis, are exciting developments that are being evaluated in clinical trials.