Myocardial infarction (MI) poses a significant burden to both patients and the health care system. The irreversible loss of functional cardiomyocytes due to ischemia threatens both patients’ immediate survival and quality of life over their lifespan. Stem cell therapy has been proposed as a solution to salvage cardiac contractility through the regeneration of cardiomyocytes, and bone marrow–derived stem cells (BMSc) are among the category of stem cells most extensively studied. Despite the promising theoretical potential of BMSc in tissue regeneration, several key aspects remain to be better understood to enable large-scale clinical application, including safety and efficacy. Our current work in synthesizing and evaluating both preclinical and clinical studies using stem cell applications in acute MI has demonstrated that BMSc transplantation is a safe therapy for MI. Although this therapy’s efficacy is not consistently proven, we have significantly improved our understanding of factors contributing to its success, such as the stem cell type, patients’ baseline left ventricular ejection fraction, individual hemodynamic factors, and differential expressions of specific genes. In future investigations, researchers should focus on the cellular and individual attributes of BMSc treatment to achieve maximal efficacy and outcomes for patients receiving this therapy after acute MI.