. and Société Française de Biochimie et Biologie Moléculaire (SFBBM) Peroxisome proliferator-activated receptors (PPARs) have emerged as key regulators of physiological and immunological processes. Recently, one of their members PPARβ/δ has been identified as major player in the maintenance of bone homeostasis, by promoting Wnt signalling activity in osteoblast and mesenchymal stem cells (MSC). PPARβ/δ not only controls the fate of MSC but also regulates their immunosuppressive properties by directly modulating their NF-κB activity. In this review, we discuss how the regulation of PPARβ/δ provides an innovative strategy for an optimisation of MSC-based therapy.