The high rate of induction of CCR by imatinib has rekindled interest in autologous stem cell collection in CML. It now is possible to collect sufficient numbers of Ph- PBSC for autologous transplantation from most patients; however, additional approaches to eliminate residual disease in autografts in a larger number of patients and to sustain cytogenetic response after transplantation of Ph- PBSC are required. Collection of autografts with low levels of BCR/ABL+ cells from imatinib-treated CML patients may allow a significantly greater chance of success for additional purging procedures. Systemic administration of imatinib, alone or in combination with other therapeutic modalities, may allow for improved maintenance of cytogenetic remission status. The clinical application of some of the promising methods reviewed here, therefore, may result in better purging of the autograft and more effective elimination of residual leukemia than has been possible to date and allow long-term restoration of Ph- hematopoiesis. It is likely that pilot studies of autologous transplantation will be limited initially to patients who have failed imatinib therapy. If successful, however, subsequent clinical trials should evaluate the use of such strategies earlier in the course of treatment of the disease, especially if better predictors of failure of imatinib treatment are available.