Acute promyelocytic leukemia (APL) represents a remarkable disease in which leukemogenesis is driven by the PML-RARα oncogene and for which targeted treatment with all-trans retinoic acid (ATRA)-based therapy allows substantial chance of cure. APL is seen in a small subset of older patients, with age representing one of the most important prognostic factors for outcome of treatment. Unlike other acute leukemias, the inferior outcomes for APL in older patients relates less to changes in disease biology and more to the increased toxicity of ATRA and the chemotherapy combination regimens used to induce hematologic and molecular responses. Risk-adapted strategies that use less-toxic agents, such as arsenic trioxide, allow treatment of older patients, with greater efficiency and better chances of cure.