Acute promyelocytic leukemia (APL) is a disease associated with fusion oncoproteins invariably involving the retinoic acid receptor (Raralpha). Retinoic acid induces differentiation in APL cells and is successfully used in conjunction with chemotherapy to treat and cure a significant percentage of patients with APL. APL is also a model for disruption of normal retinoid-mediated transcription resulting in blocked differentiation. The study of the molecular mechanisms of APL oncogenesis has revealed novel interactions between fusion oncoproteins and transcriptional coregulators, already leading to new treatment strategies.