Adipocytes arising from mesenchymal stem cells (MSCs) requires MSC adipocyte commitment and differentiation of preadipocytes to mature adipocytes. Several signaling and some cytokines affect the adipogenesis of MSCs. This review focuses on the roles of TGF-β/SMAD signaling in adipocyte commitment of MSCs. BMP4 and BMP7 signaling are sufficient to induce adipocyte lineage determination of MSCs. The roles of BMP2, TGF-β, and myostatin signaling in this process are unclear. Other TGF-β/SMAD signaling such as BMP3 and BMP6 signaling have almost no effect on commitment because of limited research available, while GDF11 signaling inhibits adipocyte commitment in human MSCs. In this review, we summarize the available information on TGF-β/SMAD signaling regulation of MSCs in adipocyte commitment. Deeper study of this commitment mechanism will offer new approaches in treating obesity, diabetes mellitus, and obesity-related metabolism syndrome.