Since 1968 hematopoietic stem cell transplantation (HSCT) has progressed from an experimental to standard therapeutic procedure. There are many obstacles to the successful outcome of HSCT procedures. Some of these obstacles are lack of healthy histocompatible donors, graft versus host disease, graft rejection and infections. Many advances have been made to overcome these obstacles with significant success. However, these issues and associated problems continue to persist at different levels as the field evolves with expanding indications for HSCT, use of alternative sources for hematopoietic stem cells and alternative transplant procedures. Newer interventions have allowed us to overcome some of these obstacles.