In the heart with atherosclerotic coronary disease, chronic ischemia causes progressive loss of cardiovascular cells and ultimately triggers myocardial dysfunctions or heart failure. Various types of stem cells from embryonic and adult tissues have potentials for regenerating functional cardiovascular cells in the heart undergoing ischemic injury. However, native or exogenous stem cells in the ischemic hearts are exposed to various proapoptotic or cytotoxic factors. Furthermore, during repopulation and differentiation, certain numbers of newly produced cells may die by apoptosis during neocardiovascular tissue remodeling and morphogenesis. Embryonic and adult stem cells may have different life spans, as being programmed genetically to apoptosis. The endogenous and environmental factors play important roles in regulation of stem cells, including inflammatory cytokines, growth factors, surface receptors, proteolytic enzymes, mitochondrial respiration, nuclear proteins, telomerase activities, hypoxia-responding proteins, and stem cell-host cell interaction. Clarification of the molecular mechanisms may help us understand and design stem cell therapies.