The finding that Endothelial progenitor cells (EPCs) can home to sites of neovascularization and differentiate into endothelial cells in situ is consistent with “vasculogenesis”, a critical paradigm well described for embryonic neovascularization, but recently also proposed for the adult organism in which a reservoir of progenitor cells contributes to post-natal neovascular formation. The discovery of EPCs has therefore drastically changed our understanding of adult blood vessel formation. Furthermore, people noticed the valuable capability to translate EPC potential to improve the clinical applicability in the fight against cardiovascular diseases. Many groups involved in clinical trials have demonstrated that EPC therapy is safe and feasible for the treatment of critical limb ischemia and cardiovascular diseases. However, many issues in the field of EPC biology, especially in regards to the proper and unambiguous molecular characterization of these cells still remain unresolved, hampering not only basic research but also the effective therapeutic use and widespread application of these cells. In this presentation, I introduce the recent concept of EPC identification in terms of hematopoietic and non-hematopoietic EPCs along with the development of EPC biology research. Furthermore, I define the role of circulating EPCs in post-natal neovascularization to illustrate the future direction of EPC therapeutic applications. I overview candidate cells for cardio- and peripheral- vascular diseases, introduce the practical example of therapeutic application of cells to ischemic disease patients and discuss the future direction.