CD34 is a cell surface antigen expressed in numerous stem/progenitor cells including hematopoietic stem cells (HSCs) and endothelial progenitor cells (EPCs), which are known to be rich sources of EPCs. Therefore, regenerative therapy using CD34 + cells has attracted interest for application in patients with various vascular, ischemic, and inflammatory diseases. CD34 + cells have recently been reported to improve therapeutic angiogenesis in a variety of diseases. Mechanistically, CD34 + cells are involved in both direct incorporation into the expanding vasculature and paracrine activity through angiogenesis, anti-inflammatory, immunomodulatory, and anti-apoptosis/fibrosis roles, which support the developing microvasculature. Preclinical, pilot, and clinical trials have well documented a track record of safety, practicality, and validity of CD34 + cell therapy in various diseases. However, the clinical application of CD34 + cell therapy has triggered scientific debates and controversies in last decade. This review covers all preexisting scientific literature and prepares an overview of the comprehensive biology of CD34 + cells as well as the preclinical/clinical details of CD34 + cell therapy for regenerative medicine.