Osteoporosis is a frequently seen metabolic bone disease characterized by reduced bone mass, reduced bone mineral density and bone micro-structure destruction. Patients with osteoporosis are prone to brittle fractures, and the incidence of osteoporosis is increased annually. The pathogenesis of osteoporosis is related to the imbalance between osteoblasts and osteoclasts. On one hand, the activity of osteoclasts is increased, with high bone resorption; on the other hand, the function of osteoblasts is attenuated, with low osteogenesis; and finally the two reasons lead to loss of net bone mass. Osteogenesis is closely related to the differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). In osteoporotic patients, the adipogenic differentiation of BMSCs is increased and the osteogenic differentiation is decreased. The differentiation fate of BMSCs is regulated by BMP/Smad, Wnt, Notch, Hedgehogs and other signal pathways, involving microRNAs, transcription factors, epigenetic and other regulatory mechanisms, which is a focus in current research. The future studies need to focus on finding the key factors in determining the differentiation fate of BMSCs and BMSCs transplantation, so as to cast new lights on the treatment of osteoporosis.