Mesenchymal stem cells (MSCs) have important roles in the area of regenerative medicine and clinical applications due to their pluripotent nature. Osteogenic differentiation of MSCs has been studied extensively using various stimulants to develop models of bone repair. There are several factors that enhance the differentiation of MSCs into bone tissues. This review focuses on the effects of various inducers on the osteoblast differentiation of MSCs at different stages of cellular development. We discuss the various growth factors, hormones, vitamins, cytokines, chemical stimulants, and mechanical forces applied in bioreactors that play an essential role in the proliferation, differentiation, and matrix mineralization of stem cells during osteogenesis. Various nanoparticles have also been used recently for the same purpose and the results are promising. Moreover, we review the role of various stresses, including thermal stress, and the subsequent involvement of heat shock proteins as inducers of the proliferation and differentiation of osteoblasts. We also report how various proteasome inhibitors have been shown to induce proliferation and osteogenic differentiation of MSCs in a number of cases. In this communication, the role of peptide-based scaffolds in osteoblast proliferation and differentiation is also reviewed. Based on the reviewed information, this article proposes novel possibilities for the enhancement of proliferation, differentiation, and migration of osteoblasts from MSCs. © 2014 S. Karger AG, Basel.