Ischemic heart and cerebral diseases are complex clinical syndromes. Endothelial dysfunction caused by dysfunctional endothelial progenitor cells (EPCs) is thought to play a major role in pathophysiology of both types of disease. Healthy EPCs may be able to replace the dysfunctional endothelium through endogenous repair mechanisms. EPC levels are changed in patients with ischemic cerebrovascular and cardiovascular disease and EPCs may play a role in the pathophysiology of these diseases. EPCs are also a marker for preventive and therapeutic interventions. Homing of EPCs to ischemic sites is a mechanism of ischemic tissue repair, and molecules such as stromal-derived factor-1 and integrin may play a role in EPC homing in ischemic disease. Potentiation of the function and numbers of EPCs as well as combining EPCs with other pharmaceutical agents may improve the condition of ischemia patients. However, the precise role of EPCs in ischemic heart and cerebral disease and their therapeutic potential still remain to be explored. Here, we discuss the identification, mobilization, and clinical implications of EPCs in ischemic diseases.