The World Health Organization Classification of Lymphoid Neoplasms identifies Burkitt lymphoma/leukemia as a highly aggressive mature B-cell neoplasm consisting of endemic, sporadic, and immunodeficiency-associated variants. These subtypes share many morphologic and immunophenotypic features, but differences exist in their clinical and geographic presentations. All of these subtypes possess chromosomal rearrangements of the c-myc oncogene, the genetic hallmark of Burkitt lymphoma that contributes to lymphomagenesis through alterations in cell cycle regulation, cellular differentiation, apoptosis, cellular adhesion, and metabolism. Brief-duration, high-intensity chemotherapy regimens containing aggressive central nervous system prophylaxis have had remarkable success in the treatment of this disease, with complete remission rates of 75% to 90% and overall survivals reaching 50% to 70% in adults. Although Burkitt lymphoma cells are extremely chemosensitive, biologically targeted therapies should be developed because current treatment options are suboptimal for patients with poor prognostic features or in the setting of relapsed disease.