High-dose chemoradiation therapy with autologous hematopoietic progenitor cell support is effective treatment for patients with a variety of high-risk malignancies. In this setting, tumor cell contamination of the hematopoietic progenitor cell product is a frequently observed problem. The malignant cells in the autograft may be a source of relapse after transplant. Purging the hematopoietic cell grafts ex-vivo may eradicate malignant cells that may contaminate the autologous product. This chapter describes the major purging strategies that have been investigated clinically over the past decade. This investigation includes negative purging with pharmacologic agents and monoclonal antibodies, positive selection with immunoadsorption, immunomagnetic and flow cytometric sorting techniques, ex-vivo culture method, treatment with cytotoxic T cells, and virally mediated purging methods.