Despite recent studies suggesting that the heart has instrinsic mechanisms of self-regeneration following myocardial infarction, it cannot regenerate itself to an optimal level. Mesenchymal stem cells (MSCs) are currently being investigated for regeneration of mesenchyme-derived tissues, such as bone, cartilage and tendon. In vitro evidence suggests that MSCs can also differentiate into cardiomyogenic and vasculogenic lineages, offering another cell source for cardiovascular regeneration. In vivo, MSCs may contribute to the re-growth and protection of vasculature and cardiomyocytes, mediated by paracrine actions, and/or persist within the myocardium in a differentiated state; although proof of cardiomyocytic phenotype and functional integration remains elusive. Herein, we review the evidence of MSCs as a cell source for cardiovascular regeneration, as well as their limitations that may prevent them from being effectively used in the clinic.