Experimental and clinical evidence for persistence of polyclonal Philadelphia chromosome negative (Ph-) progenitors in chronic myelogenous leukemia (CML) patients has provided the rationale for autologous transplantation. Clinical trials of autologous transplantation suggest that this procedure can induce cytogenetic remissions in a subset of patients and may be associated with longer-than-expected patient survival. Most autologous transplant recipients, however, continue to have evidence of persistent leukemia. Recent reports indicating that it is possible to collect sufficient numbers of Ph- peripheral blood stem cells for autologous transplantation from most patients in complete cytogenetic remission on imatinib treatment have rekindled interest in autologous transplantation in CML. Additional approaches to eliminate residual disease in autografts and to sustain cytogenetic response after transplantation, however, will be required to achieve long-term restoration of Ph- hematopoiesis. Several promising methods to improve purging of the autograft and for more effective elimination of residual leukemia are being explored.