This article focuses on the recent evolution of novel conditioning regimens in combination with adoptive cellular therapy in the allogeneic transplant setting for hematologic malignancies. Building on data from animal models, the field of allogeneic transplantation is undergoing a paradigm shift toward immunosuppressive regimens with less toxicity that allow donor hematopoietic engraftment in order to provide a graft-versus-tumor effect as the primary goal of transplantation, rather than chemoablation. In addition, the strategies described in this article, including the use of T-cell subsets as adoptive therapy, will apply to a much broader pool of patients than traditional transplant approaches, thereby allowing more patients with life-limiting illnesses, previously deemed ineligible, to pursue therapy with curative intent.