Therapy-related acute myelogenous leukemia and myelodysplastic syndrome (t-AML/MDS) are increasing in prevalence with aging of the population and improved survival of patients treated with chemotherapy or radiotherapy for other malignancies. Research focused on the pathogenesis of t-AML/MDS will provide insight into the pathogenesis of de novo AML/MDS. Participation in clinical trials should be encouraged for this patient population because results with available treatment options are clearly suboptimal.