Stem cell therapy is a promising strategy for tissue regeneration. The therapeutic benefits of cell therapy are mediated by both direct and indirect mechanisms. However, the application of stem cell therapy in the clinic is hampered by several limitations. This concise review provides a brief introduction into stem cell therapies for ischemic heart disease. It summarizes cell‐based and cell‐free paradigms, their limitations, and the benefits of using them to target disease. stem cells translational medicine 2018;7:354–359