Despite extensive medical advances, stroke is still one of the major problems in health care system. Researchers are seeking novel therapeutic strategies for the treatment of stroke, such as cell-therapy. In this regard, mesenchymal stem cells are the most used cells in stroke cell-therapy researches. Mesenchymal stem cells are multipotent cells capable of self-renewal and differentiation, which can be derived from various tissues, such as bone marrow, skeletal muscle, adipose tissue, umbilical cord, and synovium. In this review article, after description of mesenchymal stem cells, the studies related to use of these cells in stroke as well as the challenges ahead in the field of stroke cell therapy, were mentioned. According to existing studies, although it seems that use of mesenchymal stem cells transplantation has a bright prospect in the treatment of stroke, there are still some issues, such as apoptosis of grafted cell, neural differentiation of stem cell, likelihood of malignancy of transplanted cell, unwanted cell differentiation, and migration to ischemic region, have overshadowed its clinical application.