AbstractEfforts to develop curative treatment strategies for chronic lymphocytic leukemia (CLL) in recent years have focused on allogeneic stem cell transplantation (alloSCT). The crucial anti-leukemic principle of alloSCT in CLL appears to be the immune-mediated anti-host activities conferred with the graft (graft-versus-leukemia effects, GVL). Evidence for GVL in CLL is provided by studies analyzing the kinetics of minimal residual disease on response to immune modulation after transplantation, suggesting that GVL can result in complete and durable suppression of the leukemic clone. AlloSCT from matched related or unrelated donors can overcome the treatment resistance of poor-risk CLL, ie, purine analogue refractory disease and CLL with del 17p-. Even with reduced-intensity conditioning, alloSCT in CLL is associated with significant mortality and morbidity due to graft-versus-host disease, which has to be weighed against the risk of the disease when defining the indication for transplantation. Therefore, it can be regarded as a reasonable treatment option only for eligible patients who fulfill accepted criteria for poor-risk disease. If alloSCT is considered, it should be performed before CLL has advanced to a status of complete refractoriness to assure an optimum chance for a successful outcome. Prospective trials are underway to prove whether allo-SCT can indeed change the natural history of poor-risk CLL.