AbstractGraft-versus-tumor effect is well recognized in allogeneic transplantation, but it appears to be disease specific and relapse remains a significant problem. Furthermore, immune reconstitution after hematopoietic cell transplantation is often delayed and incomplete. It is becoming increasingly clear that the immune system is complex and that cooperation between innate and adaptive immunity is required to induce a productive immune response. Progress in clinically applicable cell separation techniques and knowledge of the signals required for effective immune activation have made adoptive therapy with T cells and NK cells a viable treatment option. However, clinical efficacy with either cell type depends on in vivo expansion of the infused product, which is facilitated through mechanisms that are active after lymphodeletion. Although successes have been seen with several approaches, further study of immune biology, lymphocyte cooperation and the role of regulatory T cells will lead to better strategies to exploit adoptive transfer of lymphocytes for therapeutic benefit.