Solid organ transplantation (SOT) currently represents the best therapeutic option in end-stage diseases caused by the irrevocable functional loss of an organ. Still, SOT is associated with immunological and non-immunological injuries, whose severity impacts on early functional recovery and long-term survival of the transplant. Current research focuses on the identification of innovative approaches to 1) attenuate ischemia/reperfusion-induced damage, 2) accelerate processes of tissue repair, and 3) induce in fine graft tolerance. Encouraging observations from both preclinical studies and clinical trials suggest that the administration of mesenchymal stromal cells at the time of SOT might be beneficial, as a result of theirs immunomodulatory, anti-inflammatory and regenerative properties.