Mesenchymal stem cells (MSCs) have been recognized as the best candidate for tissue engineering, while the mechanism of biomaterial-induced MSCs differentiation is not well understood. Most of research has been focused on chemical signaling of biomaterial in the past, but a variety of non-chemical signals were also proved to play essential roles in cellular behaviors. In this paper, we reviewed the current reports about the effects of different kinds of biomaterial signals on MSCs differentiation.