In the context of a growing pandemic of myocardial infarction (MI), the current standard therapies cannot provide an ideal outcome for the patients. Hence, novel approaches are being explored to identify curative treatment. In recent years, stem cell has been regarded as a critical source for cardiac regeneration, and several types of stem cells have been demonstrated with cardiogenic capacity. To date, thousands of patients with MI have received autologous stem cells therapy, but the benefits were modest. In this review, we summarize the recent findings of stem cells therapy in cardiac repair and regeneration, and propose the key unsolved hurdles in this field.