Hillary Stoll, Frederick G Hamel, Jeong Soon Lee, Ligyeom Ha and Jung Yul LimIncreased Mesenchymal Stem Cell (MSC) commitment and differentiation into adipocytes contributes to obesity. Other than dietary and biochemical factors, recent studies have begun to explore the role of mechanical signals in controlling MSC adipocytic commitment and differentiation. Several reported data suggest that by subjecting MSCs to certain mechanical stimuli, such as stretching, compression, and fluid shear, their adipogenesis could be inhibited or decreased. However, it is still very early to draw conclusions on the detailed mechanical regimens to optimally inhibit MSC adipogenesis and on the molecular pathways governing such adipogenesis-inhibitory mechanosensitive signaling. In this commentary, key data on the mechanical control of MSC adipogenesis and proposed molecular mechanisms will be highlighted and a future perspective in this new topic area will be provided.