The pluripotent mesenchymal stem cells (MSC) are common precursors to adipocytes and osteoblasts. Large numbers of extracellular and intracellular signals and transcription factors moderate adipogenesis and osteoblastogenesis. Importantly, between adipogenic and osteogenic lineage commitment and differentiation, differentiation of MSCs into one lineage will inhibit their differentiation toward the other lineage. This balance is regulated by numerous signaling pathways. As we know, the peroxisome-proliferator-activated receptor-γ (PPAR-γ) and Wnt/β-catenin pathway are regarded as the master moderators of adipogenesis and osteogenesis. Moreover, governing the differentiation of MSCs to adipogenesis and osteoblastogenesis has significant implications in diverse areas of human health, from obesity to regenerative medicine to osteoporosis. Rivalry roles have been reported of the two pathways since the downstream products activated by Wnt-5a repress PPAR-γ transactivation through the H3K9 histone methyltransferase protein complexes. This review will discuss the inductive and inhibitive role of PPAR-γ in adipogenesis and osteoblastogenesis respectively, as well as the canonical Wnt/β-catenin pathway.