Acute lymphoblastic leukemia and lymphoblastic lymphoma constitute a family of genetically heterogeneous lymphoid neoplasms derived from B- and T-lymphoid progenitors. Diagnosis is based on morphologic, immunophenotypic, and genetic features that allow differentiation from normal progenitors and other hematopoietic and nonhematopoietic neoplasms. Current intensive chemotherapy regimens have accomplished overall cure rates of 85% to 90% in children and 40% to 50% in adults, with outcomes depending on the genetic subtype of disease and clinical features at presentation. Therapy is optimized using minimal residual disease studies that employ flow cytometric and molecular methodologies, and are important determinants of prognosis. Genetic analyses currently underway are likely to provide insight into biology, mechanisms of relapse, pharmacogenetics, and new potential therapeutic targets, which should aid in further improvement of outcome in this disease.