Cardiovascular-renal diseases are the leading causes of death and disability in the modern world. Moreover, chronic heart failure after myocardial infarction and peripheral arterial disease are predominant, devastating cardiovascular entities that limit prognosis and greatly impair quality of life in patients despite modern medical treatments. Cardiovascular diseases are also the predominant cause of death in people with renal diseases, underscoring the close relationship between these diseases. Until recently, medical efforts aimed only at prevention and slowing of functional deterioration after organ damage; however, the recent discovery of endogenous repair mechanisms involving hematopoietic stem and other progenitor cells has challenged the long-standing dogma regarding the inability to repair or regenerate terminally differentiated organs. A variety of stem and progenitor cell populations have shown properties that are potentially suited for tissue repair. After encouraging results in preclinical animal models, early clinical studies of endothelial progenitor cells (EPC) have begun. Envisioning the goal of true tissue regeneration, application of bone marrow-derived progenitors for heart and limb ischemia has provided early evidence of safety and feasibility. These studies have provided data indicating functional improvement as well. Although there is strong experimental and clinical evidence for a regenerative function of EPC even in renal disease, there has been no clinical application of this approach. After the initial flurry of activity, it is time to reconsider these approaches and attempt to optimize functional improvement and patient safety. This article briefly recapitulates biologic and functional characteristics of EPC before giving a concise overview on current therapeutic EPC applications in the field of cardiovascular-renal medicine with consideration of future challenges.