Osteogenic differentiation of mesenchymal stem cells (MSCs) is an important link of bone metabolism and bone repair, the mechanism of which is usually complicated. Recent studies have found that BMP, FGF, Wnt, Hedgehog, NELL1, IGF, Notch and other signaling molecules are involved in the regulation of osteogenic differentiation of MSCs. These signaling molecules themselves have been shown to have a strong ability to promote osteogenic differentiation. They can activate the corresponding receptors by specific ligands, thus initiating the specific signal transduction pathways in the cell, and finally promote the transcription and translation of the genes related to bone formation. Furthermore, all the signaling pathways form a complex network which regulates and influences the osteogenic differentiation of MSCs. Further researches on the mechanism of the interaction of these signaling pathways is of great significance in promoting the development of bone tissue engineering and the treatment of bone metabolic diseases.