Mesenchymal Stem Cells (MSCs) are self-renewing cells with ability to differentiate into organized, functional network of cells. In recent past research in developing clinical applications for MSCs has increased significantly. MSCs exhibit multi potential proliferation, and are capable of differentiating into cartilage, bone, neuronal cells and adipocytes, etc. Signaling pathways, transcription factors and growth factors modulate the differentiation of MSCs into different cell lineages. Besides, physical factors may regulate the molecular differentiation of stem cells. The main theme of this paper is to review the signaling pathways related to bone morphogenetic proteins (BMPs), epidermal growth factors (EGF), transforming growth factors (TGF), wingless type MMTV integration site (wnt) proteins, fibroblastic growth factor (FGF), and transcriptional regulating factors significance in the MSCs differentiation.