Considerable hope has been vested in cell therapy strategies designed to augment the endogenous neovascularization response to obstructive coronary artery disease, and to replace cardiomyocyte loss caused by myocardial infarction. Conceptually, the relative importance of targeting angiogenesis versus myogenesis in this scheme will vary depending on the clinical context (the predominance of ischemia versus ventricular dysfunction and scarring). Although the evidence so far is encouraging, whether these processes can be effectively targeted in a selective fashion with cell therapy is still unclear. Intriguingly, data are now emerging suggesting that the beneficial effects of cardiac cell therapies in a variety of clinical settings may be accounted for by a greater interaction of angiogenesis, myocardial salvage and myogenesis than heretofore appreciated, and through mechanisms that may include both cellular and paracrine effects. Greater understanding of these mechanisms should accelerate the development of effective cell therapies for the growing number of patients with advanced, and in many cases 'no-option', cardiovascular disease. Possible clinical targets for angiogenic and myogenic cardiac cell therapy, the scientific rationale for this therapeutic approach and future directions in this field are discussed here.