The mammalian heart has long been considered a post-mitotic organ with limited regenerative capacity. However, recent discoveries have challenged this notion, revealing the existence of precursor cell populations that can contribute to cardiac repair. These populations include cardiac progenitors resident in the adult heart, non-cardiac multipotent stem cells, and reprogrammed cardiac cells generated from non-cardiac lineages. These progenitor cells can mediate cardiac regeneration either through direct cell differentiation or through indirect paracrine signals that stimulate endogenous repair. Numerous studies have reported the feasibility and relative safety profile of stem cell-based transplantation therapies in cardiovascular disease (CVD). While promising potential for therapeutic benefit exists, ongoing research is crucial to fully validate efficacy for clinical translation. This is in line with advancements in tissue engineering platforms to optimize cell delivery and enhance therapeutic outcomes. In addition to therapy, stem cells offer promise in applications such as disease modeling and personalized medicine, offering broader insights into CVD. In this chapter, we review the fundamental aspects of cardiac stem cell biology and its applications in cardiovascular therapy and beyond, with a critical examination of the current evidence, limitations, and future perspectives.