Burkitt lymphoma/leukemia (BL) has become a very curable mature B-cell neoplasm. Current standard regimens, focused on the unique characteristics of this disease, are composed of cyclical intensive chemotherapy and aggressive intrathecal prophylaxis. Using this approach, complete response rates of 80%-90% are routinely achieved, and survival is now approaching 80% with the addition of rituximab to these intensive regimens. Prophylactic cranial irradiation and prolonged maintenance have no proven benefit and are not recommended. The more widespread use of highly active antiretroviral therapy in the HIV patient with BL has allowed the use of similar aggressive therapies that are used for the non-HIV BL patients, with commensurate improvements in outcomes in this high-risk population. Future improvements for patients with BL could rely on standardization of gene expression profiling (to ensure more accurate diagnoses and prognostication of disease and to understand mechanisms of treatment resistance) and to develop novel biologically targeted approaches to treatment. The next generation of clinical trials to further improve survival will have the challenge of identifying high-risk patients who might be candidates for novel agents that could be incorporated into existing regimens with the goal of curing all patients with this disease.