Purpose of review Treatment with classical immunosuppressive drugs is associated with low specificity leading to toxicity, infections and malignancies. Cell therapy is emerging as an alternative for the pharmacological therapies and among them mesenchymal stem cells (MSCs) appear as a solid choice for the treatment of transplanted patients. The aim of the present review is to analyze the potency of MSCs cell therapy in solid organ transplantation. Recent findings The increasing knowledge on the role of newly identified cell types like the pro-inflammatory Th17 cells, tolerogenic dendritic cells, regulatory macrophages and regulatory B cells among others in alloreactivity widened our understanding of the immune responses in transplantation patients. Recent studies suggest that MSCs interact with those populations as well as with classically studied Th1 cells to reduce alloreactivity and potentially promote graft acceptance. Summary MSCs are arising as an immunomodulatory and potentially pro-tolerogenic tool in cell therapeutic intervention in solid organ transplantation and could substitute or minimize current immunosuppressive treatments.