With better understanding of endothelial progenitor cells (EPCs), many therapeutic approaches to cardiovascular diseases have been developed. This article will review novel research of EPCs in promoting angiogenesis, vasculogenesis, and endothelialization, as a design for future clinical treatment. Cell therapy has the potential to supply stem/progenitor cells and multiple angiogenic factors to the region of ischemia. The efficacy of EPC transplantation may be impaired by low survival rate, insufficient cell number, and impaired function in aging and diseases. Combination of EPCs or cells primed with growth factors or genetic modification may improve the therapeutic efficacy. The molecular mechanism involved in EPC repairing processes is essential. Thus, we have also addressed the molecular mechanism of mobilization, homing, and differentiation of EPCs. The potential of therapeutic neovascularization, angiogenic factor therapy, and cell transplantation have been elucidated. Based on past experience and actual knowledge, future strategies for EPC therapy will be proposed in order to fully exploit the potential of EPC transplantation with clinical relevance for cardiovascular disease applications.