Over the last 25 years, allogeneic hematopoietic stem cell transplantation (HSCT) has been used increasingly as a curative treatment option for patients with hematologic and neoplastic diseases. Despite major advances in transplant immunology and improvements in supportive and critical care medicine, HSCT is still plagued by several life-threatening complications. As such, the establishment of effective therapeutic options for these complications will be crucial as increasing numbers of high-risk transplants are performed each year. This brief review will discuss the contribution of vascular endothelial cell activation and injury to inflammation and end-organ toxicity that occurs following allogeneic HSCT, and will highlight translational research efforts that have paved the way to the development of novel strategies to treat and prevent disease. Finally, we will discuss in detail the clinical manifestations and challenges encompassed by the syndrome of thrombotic microangiopathy following HSCT.