The success of hematoablative dosages of cytotoxic therapy followed by stem cell transplantation depends on the disease response to the intensive drug dose and the ability of the transplant to provide durable hematopoietic reconstitution. In autologous stem cell transplantation, patients' own bone marrow or peripheral blood is used for hematopoietic engraftment. In several diseases the bone marrow is involved, and in such situations, the success of autologous stem cell transplantation may improve if the hematopoietic elements are enriched (positive selection) or if the contaminating cancer cells are purged by negative selection. In patients undergoing allogeneic bone marrow transplantation, the T lymphocytes of the donor cells contribute to the development of graft-versus-host disease with significant morbidity and mortality. Selective purging of T lymphocytes has dramatically decreased the incidence of graft-versus-host disease. In this paper, various methods for purging hematopoietic stem cells are detailed with emphasis on treatment planning. Exciting new possibilities include growing stem cells from a small amount of bone marrow, enhancing immune surveillance, and decreasing drug resistance by genetic engineering.