Although hemopoietic stem cell transplantation (HSCT) is one of the major success stories of modern medicine, it remains a high-risk procedure that often causes life-threatening or life-changing toxic effects. The early pioneering transplants during the late 1960s and throughout the 1970s were complicated by a high incidence of severe conditioning regimen-related toxic effects, infections, and graft-vs-host disease (GvHD), leading to high treatment-related early mortality rates. Subsequently, major advances in transplantation science, especially concerning histocompatibility testing and immunosuppressive strategies, have increased donor availability and consolidated the role of HSCT in the treatment of many lethal or life-limiting hematological, immunological, and metabolic diseases. At the same time, remarkable improvements in supportive care have enabled prevention, earlier diagnosis, and more effective treatment of severe infections and other acute life-threatening complications, thereby reducing early transplant-related mortality. Every year, HSCT now cures thousands of patients with previously fatal illnesses.