The vast majority of adults with acute lymphoblastic leukemia (ALL) now achieve remission with current intensive chemotherapy regimens. Nevertheless, most adults with ALL will eventually relapse and die of their disease. Specific clinical and molecular-cytogenetic prognostic factors have been identified that are beginning to provide insights for the development of risk-adapted management strategies that appear to improve survival for several high-risk patient groups, including those with mature B-cell ALL and B-lineage ALL patients with a Philadelphia chromosome. We review standard and some recently described prognostic factors in adult ALL, describe current therapy based on a risk-adapted approach, and look toward the future with a brief discussion of novel, targeted treatments that could be incorporated into postremission strategies to improve survival for adults with ALL.