In the 60 years since the recognition of acute promyelocytic leukemia as a distinct entity, outcomes for patients have improved dramatically. This has occurred partly because of improvements in supportive care, and partly because treatment has diverged from reliance on standard antileukemic chemotherapy to the use of agents that are specifically targeted at the molecular events responsible for initiating and maintaining the disease. However early death remains a significant barrier to cure, especially for patients who fall outside the selection biases imposed by clinical trials. This review will focus on changes to clinical practice that have been adopted to reduce the risk of failure.