Acute lymphoblastic leukemia (ALL) is typically treated with complex multi-agent chemotherapy regimens over a prolonged time period. Long-term outcomes depend on the age of the patient and the biological characteristics of the leukemic cells. While pediatric patients achieve cure more often than adults, therapy can continue to be improved for all patients with this disease.The current management strategy for ALL is reviewed. Recently, targeted therapies have been shown to improve survival in subsets of patients, most notably in those with Philadelphia chromosome-positive ALL or with leukemic cells that express the surface antigen CD20. Several innovative compounds are under investigation, and the most promising ones to date will be discussed.The incorporation of monoclonal antibody therapy represents a targeted and powerful approach to the management of ALL. Bispecific T-cell engaging agents, such as blinatumomab, are able to facilitate immune-mediated killing of leukemia cells. Immunoconjugates (i.e., monoclonal antibodies linked to various cytotoxins) allow small doses of very potent chemotherapy to be delivered directly to a leukemia cell with hope of sparing normal tissue. As the genetic and molecular characterization of ALL is more completely understood, patients will receive treatment plans that are more individualized than previously possible.