Bone marrow transplantation (BMT) is a potentially curative therapy for a number of life-threatening hematologic malignancies; however, the subsequent development of severe graft-vs.-host disease (GVHD) remains a major obstacle, impeding its widespread application. Prevention and treatment of GVHD may involve modulating the host/donor cellular environment following BMT. Suspected mechanisms by which cells with immunoregulatory properties inhibit alloresponses include natural suppressor and veto activity. Cell phenotypes associated with suppressive activity in mice and humans include null cells, double negative T lymphocytes, and natural killer cells. Cellular-based therapies for the treatment of acute GVHD using autologous peripheral blood mononuclear or bone marrow cells have shown promise in reversing GVHD following allogeneic transplantation. In this review, we examine the considerable evidence supporting an immunoregulatory role for both host and donor cells in modulating acute GVHD.