Ischemic cardiovascular diseases cause a significant burden of morbidity and mortality throughout the world. Over the past decade, we have learned a tremendous amount about the biology of various stem and progenitor cells. Multiple preclinical experiments have demonstrated significant bioactivity in a wide variety of stem and progenitor cells. Early clinical trials have also shown some promising results. This review will focus on the current challenges in the translation of cell therapy to a viable clinical therapy. Additionally, we will highlight the role of cardiovascular imaging and molecular imaging in the future of stem cell therapy.