Adult stem cells have been proven to possess tremendous potential in the treatment of hematological disorders, possibly in transplantation. Mesenchymal stem cells (MSCs) are a heterogeneous group of cells in culture, with hypoimmunogenic character to avoid alloreactive T-cell recognition as well as inhibition of T-cell proliferation. Numerous experimental findings have shown that MSCs also possess the ability to promote engraftment of donor cells and to accelerate the speed of hematological recovery. Despite that the exact mechanism remains unclear, the therapeutic ability of MSCs on hematologic transplantation have been tested in preclinical trials. Based on encouraging preliminary findings, MSCs might become a potentially efficacious tool in the therapeutic options available to treat and cure hematological malignancies and nonmalignant disorders. The molecular mechanisms behind the real efficacy of MSCs on promoting engraftment and accelerating hematological recovery are awaiting clarification. It is hypothesized that direct cell-to-cell contact, paracrine factors, extracellular matrix scaffold, BM homing capability, and endogenous metabolites of immunologic and nonimmunologic elements are involved in the interactions between MSCs and HSCs. This review focuses on recent experimental and clinical findings related to MSCs, highlighting their roles in promoting engraftment, hematopoietic recovery, and GvHD/graft rejection prevention after HSCT, discussing the potential clinical applications of MSC-based treatment strategies in the context of hematological transplantation.