There is currently major interest to use mesenchymal stromal cells (MSCs) for a very diverse range of therapeutic applications. This stems mainly from the immunosuppressive qualities and differentiation capacity of these cells. In this review, we focus on cell therapy applications for MSCs in hematology. In this domain, MSCs are used for the treatment or prevention of graft-versus-host disease, support of hematopoiesis, or repair of tissue toxicities after hematopoietic cell transplantation. We critically review the accumulating clinical data and elaborate on complications that might arise from treatment with MSCs. In addition, we assume that the real clinical benefit of using MSCs for these purposes can only be estimated by a better understanding of the influence of in vitro expansion on the biological properties of these cells as well as by more harmonization of the currently used expansion protocols.