Mesenchymal stem cells (MSCs) are multipotent cells capable of differentiating into adipocytes and osteoblasts. The balance between adipogenic and osteogenic differentiation is delicately regulated by various external cues, including chemical, physical, and biological factors. These factors trigger signaling pathways and activate transcription factors that guide MSCs to commit to either lineage. Dysregulation of this balance has been linked to several pathophysiological processes, such as aging, obesity, osteopenia, osteopetrosis, and osteoporosis. This review discusses the signaling mechanisms involved in adipogenesis and osteogenesis, and the factors that determine the lineage commitment of MSCs. Key signaling pathways include TGFβ/BMP, Wnt, Notch, and Hedgehog, which regulate the expression of transcription factors such as Runx2, PPARγ, C/EBPs, and Osterix. Chemical factors, such as IBMX, Dex, and βGP, and physical factors, such as cell shape, mechanical forces, and extracellular matrix, also play crucial roles in MSC differentiation. Biological factors, including aging and metabolism, further influence the balance between adipogenic and osteogenic differentiation. Understanding these regulatory mechanisms is essential for developing therapeutic strategies for bone diseases and other conditions related to MSC lineage commitment.Mesenchymal stem cells (MSCs) are multipotent cells capable of differentiating into adipocytes and osteoblasts. The balance between adipogenic and osteogenic differentiation is delicately regulated by various external cues, including chemical, physical, and biological factors. These factors trigger signaling pathways and activate transcription factors that guide MSCs to commit to either lineage. Dysregulation of this balance has been linked to several pathophysiological processes, such as aging, obesity, osteopenia, osteopetrosis, and osteoporosis. This review discusses the signaling mechanisms involved in adipogenesis and osteogenesis, and the factors that determine the lineage commitment of MSCs. Key signaling pathways include TGFβ/BMP, Wnt, Notch, and Hedgehog, which regulate the expression of transcription factors such as Runx2, PPARγ, C/EBPs, and Osterix. Chemical factors, such as IBMX, Dex, and βGP, and physical factors, such as cell shape, mechanical forces, and extracellular matrix, also play crucial roles in MSC differentiation. Biological factors, including aging and metabolism, further influence the balance between adipogenic and osteogenic differentiation. Understanding these regulatory mechanisms is essential for developing therapeutic strategies for bone diseases and other conditions related to MSC lineage commitment.