This review focuses on recent developments in allogeneic hematopoietic stem cell transplantation in which improved understanding and control of immune modulation have led to nonmyeloablative conditioning regimens to establish allografts. By relying on a graft-versus-tumor effect for tumor eradication, these innovative approaches reduce the toxicity barrier posed by standard allogeneic transplantation. Consequently, they can be applied to a broader population of patients including older patients with hematologic malignancies and patients with diseases not traditionally treated with allogeneic transplantation, but who may potentially benefit or be cured by an allogeneic graft-versus-tumor effect.