The success of autologous stem cell transplantation using bone marrow or peripheral blood stem cells depends not only on in vivo irradication of the disease by cytotoxic therapy but also on complete hematopoietic engraftment with no risk of relapse from the infused cells. Various methods are available for removing (purging) such contaminants. Purging techniques were developed by use of various in vitro models utilizing cell lines and fresh cancer cells. Once effective conditions were developed, they were advanced onto clinical trials. Various approaches for purging have been used. Subgroups of leukemia and lymphoma have now shown clinical benefit by the use of purged stem cells. Emphasis is now being placed on utilizing the information already obtained by the pre-clinical investigators on designing better clinical trials.