In this episode of the VJHemOnc Podcast, we focus on the management and prevention of differentiation syndrome in acute promyelocytic leukemia (APL). We begin with a discussion with Yasmin Abaza, MD, Northwestern University Feinberg School of Medicine, Chicago, IL, on the biological basis of differentiation syndrome, the rationale and mechanism behind steroid prophylaxis, and how the supporting evidence has developed over time. Yannis Valtis, MD, Memorial Sloan Kettering Cancer Center, New York, NY, then briefly comments on emerging therapeutic approaches and the need for prospective trials to better define their role.