Allogeneic (haploidentical) hematopoietic blood stem cell transplantation (allo-HSCT) is one of the main therapies for patients with malignant diseases of the blood system in children and adults with poor prognosis. The indications for allo-HSCT could not be extended due to a high risk of complications that are still associated with transplantation of hematopoietic stem cells. Non-engraftment of the hematopoietic stem cells leads to high morbidity and mortality as a result of infectious complications along with long-term neutropenia and organ dysfunctions resulting from the toxicity of the drugs used in the conditioning regimen. Graft-versus-host disease (GVHD) is one of the common, and in some cases fatal, complications of allo-HSCT. Current medicinal methods of treatment and prevention of graft failure and GVHD do not always achieve a clinical effect. One of the promising strategies for reducing the severity of GVHD is the use of mesenchymal stem cells (MSCs), which have tolerogenic characteristics. In addition, the ability of MSCs to stimulate hematopoiesis by producing a number of growth factors makes the basis for their use in case of graft failure. In general, numerous clinical studies have shown the effectiveness of this strategy. However, contradictory results and lack of standard conditions for MSC culture and the need for therapeutic regimens are the main reasons why the researchers cannot make a final conclusion about the MSC perspectives in the treatment and prevention of transplant failure and GVHD.