Stem cell biology holds great promise for a new era of cell-based therapy, sparking considerable interest among scientists, clinicians, and their patients. However, the translational arm of stem cell science is in a relatively primitive state. Although a number of clinical studies have been initiated, the early returns point to several inherent problems. In this regard, the clinical potential of stem cells can only be fully realized by the identification of the key barriers to clinical implementation. Here, we examine experimental paradigms to address the critical steps in the transition from stem cell biology to regenerative medicine, utilizing cardiovascular disease as a case study.