Stem cell transplantation (SCT) can be used to cure or ameliorate a wide variety of non-malignant diseases. These range from inherent defects of haemopoietic cell production or function, through metabolic diseases (where blood cells are providing in vivo enzyme therapy to solid organs), to severe autoimmune diseases. However, although transplantation has revolutionized the treatment of many of the diseases discussed, severe toxicities remain. In some cases these are inherent to the disease concerned but frequently they relate to the conditioning regime or post-transplant complications such as graft-versus-host disease (GvHD). This chapter concentrates on the indications for transplant, outcome statistics and problems inherent in particular conditions, seen in the light of technological improvements during the 1990s and the potential impact of enzyme and gene therapies.