Cell-based myocardial regeneration has emerged as a promising therapeutic option for ischemic heart disease, though not yet at the level of routine clinical utility. Despite the encouraging results from initial preclinical studies that have demonstrated improved function and reduced infarct size of the ischemic myocardium following several candidate cell transplantation, the beneficial effects and molecular mechanisms of cardiac cell therapy are still unclear in clinical applications to date, and much remains to be optimized. To improve engraftment, accurate methods are required for tracking cell fate and quantifying functional outcome. In the present review, we summarized the current status and challenges of cardiac cell therapy for ischemic heart disease and discussed the strengths and limitations of currently available in vivo imaging techniques with special focus on the newly developed multimodality approaches for assessing the efficacy of engrafted donor cells. We also addressed the hurdles these imaging modalities are facing, including issues regarding immunogenicity and tumorigenicity of transplanted stem cells, and provided some the future perspectives on stem cell imaging.