Hepatic venocclusive disease (VOD) is a common toxicity associated with myeloablative chemotherapy or chemoradiotherapy used to prepare patients for stem cell transplantation. A sizable proportion of patients who develop VOD die. It is clear that injury to endothelial cells and hepatocytes in zone 3 of the liver acinus is the initial event in the pathogenesis of VOD. What are less clear are the mechanisms of injury and whether this knowledge can be exploited. This manuscript will briefly review some recent data and discuss how that information has influenced clinical practice.