The new civil wars and waves of terrorism are causing crucial social changes, with consequences in all fields, including health care. In particular, skin injuries are evolving as an epidemic issue. From a physiological standpoint, although wound repair takes place more rapidly in the skin than in other tissues, it is still a complex organ to reconstruct. Genetic and clinical variables, such as diabetes, smoking, and inflammatory/immunological pathologies, are also important risk factors limiting the regenerative potential of many therapeutic applications. Therefore, optimization of current clinical strategies is critical. Here we summarize the current state of the field by focusing on stem cell therapy applications in wound healing, with an emphasis on current clinical approaches being developed at Sapienza University. These involve protocols for the ex vivo expansion of adipose tissue–derived mesenchymal stem cells by means of a patented GMP-compliant platelet lysate, Mesengen™. A combination of multiple strategies, including genetic modifications of stem cells, biomimetic scaffolds, or novel vehicles such as nanoparticles, are also discussed as future approaches.