Pluripotent stem cells (PSCs), including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have promise in regenerative medicine for a variety of applications. Their potential in the treatment of cardiovascular disease is of particular interest due to its severity and prevalence. In order to be successful for cell therapy, PSCs must be pre-differentiated into cardiomyocytes to prevent teratoma formation in vivo. Current methods focus on the supplementation of soluble factors to culture medium to drive differentiation into mesodermal lineages; however, these methods are costly with varying cardiomyocyte yields. Since cardiomyocytes are exposed to dynamic environments in vivo, there is potential in using mechanical stimulation to further drive differentiation in vitro. In this review, we will describe the most recent developments in how mechanical stimulation, including fluid shear, cyclic strain, and magnetically mediated strain, can guide cardiomyogenesis in PSCs. (c) 2013 American Institute of Chemical Engineers Biotechnol. Prog., 29:1089-1096, 2013