Bone marrow-derived CD34+ cells are a well-characterized population of stem cells that have traditionally been used clinically to reconstitute the hematopoietic system after radiation or chemotherapy. More recently, CD34+ cells have also been shown to induce therapeutic angiogenesis in animal models of myocardial, peripheral, and cerebral ischemia. The mechanism by which CD34+ cells promote therapeutic angiogenesis is not completely understood, although evidence supports both direct incorporation of the cells into the expanding vasculature and paracrine secretion of angiogenic growth factors that support the developing microvasculature. Phase I and phase II clinical trials have explored the usefulness of CD34+ cells in the treatment of ischemic conditions in human patients. As the population of patients diagnosed with some form of ischemic cardiovascular disease expands, the need for more effective treatments also grows, especially in patients who are refractory to standard pharmacologic or revascularization treatment. As phase III trials begin, CD34+ cells will be definitively tested as a novel treatment for myocardial and peripheral ischemia. This review will discuss what is known about the CD34 antigen and the cells that harbor it, the preclinical evidence supporting the therapeutic potential of CD34+ cells in ischemic models, and, last, the current evidence for the clinical usefulness of CD34+ cells in the treatment of human ischemic disease.