Recent years have brought major strides to our understanding of prognostic pathobiologic factors in patients with chronic lymphocytic leukemia. This has allowed identification of high-risk patients who may benefit from more aggressive therapies, including hematopoietic cell transplantation. High-dose chemotherapy followed by autologous hematopoietic cell transplantation is feasible, and results in encouraging responses, including molecular responses, with low transplant-associated mortality. However, it has failed to show a plateau effect on survival curves. On the other hand, there is convincing evidence that immunologically mediated graft-versus-leukemia effect of donor T cells are responsible for lowering the incidence of relapse and allowing possible "cure" in allograft recipients, albeit at the expense of high treatment-associated mortality using conventional myeloablation. Reducing the intensity of conditioning regimens has translated into lesser toxicity with reasonable preservation of its curative potential. Autologous or allogeneic hematopoietic cell transplantation in high-risk chronic lymphocytic leukemia remain promising and evolving treatment options. Treatment of CLL should consider stratification according to modern prognostic markers.