Abstract: Cardiovascular disease (CVD) is the leading cause of mortality with changing lifestyles and aging problems. But the rapid development of modern technology still cannot meet the need for diagnosis and treatment of myocardial infarction. Stem cell therapy offers renewed hope for cardiac regeneration. Compared with other adult stem cells, endogenous cardiac stem cells (CSCs) can differentiate into cardiomyocytes and vascular endothelial cells, thus having the potential to repair damaged cardiac cells. Research has shown that multiple factors are involved in the process of CSCs activation. In recent years, endogenous CSC-mediated cardiac repair has become the new focus in fields of cardiac regeneration and tissue engineering. In this review, we discuss the main pathways that mediate CSCs activation so as to elucidate in vivo functions of endogenous CSCs.