In this installment of the “How I Treat” series in the journal Blood, Dr. Nicola Gökbuget outlines how improved supportive care, targeted therapies, moderately intensified consolidation, and reduced-intensity hematopoietic cell transplantation have improved outcomes somewhat for older patients with acute lymphoblastic leukemia (ALL). But she also notes that older patients with ALL still have a significantly lower complete remission rate, higher early mortality, higher relapse rate, and poorer survival compared to younger patients. She recommends that physicians differentiate between fit and unfit older patients in order to offer both groups optimal treatment regarding toxicity and mortality risks, quality of life, and long-term outcome.