Although the median age for adults with acute lymphoblastic leukemia (ALL) is older than 60 years, relatively few of these patients have been enrolled on prospective clinical trials. The presence of coexisting medical disorders and unfavorable cytogenetic and biologic disease characteristics within this population presents considerable challenges for successful treatment using conventional chemotherapy programs. Selected patients have achieved remission and long-term survival following intensive chemotherapy. Philadelphia (Ph) chromosome (BCR/ABL)-positive ALL is particularly common among older patients. The availability of specific tyrosine kinase inhibitors is changing the prognosis for this challenging subset.