Approximately half of all adults with acute lymphoblastic leukemia now survive long term. This article summarizes the current approaches to treating acute lymphoblastic leukemia in adults, with a focus on a pragmatic approach to decision making. Coupled with a particularly punishing and often complex combination chemotherapy treatment regimen, treatment-related morbidity and mortality are frequent, and this article focuses on these situations. The field will change significantly over the next few years with many ongoing clinical studies and molecular insights which will be translated into providing prognostic information and novel therapeutic targets.