Endothelial cell markers are membrane-bound or cytoplasmic molecules expressed by endothelial cells, which help their easier identification and discrimination from other cell types. During vasculogenesis, endothelial cells differentiate from hemangioblasts to form new blood vessels. With the discovery of endothelial progenitor cells (EPC) and their ability to form new blood vessels, the term vasculogenesis is not only reserved for the embryonic development. Possibility of de novo blood vessel formation from EPC is now widely explored in different ischemic conditions, especially in cardiovascular medicine. Numerous clinical trials have tested enhancing tissue vascularization by delivering hematopoietic cells that expressed endothelial markers. This therapeutic approach proved to be challenging and promising, particularly for patients who have exhausted all conventional therapeutic modalities. Angiogenesis, which refers to the formation of new blood vessels from existing vasculature, is indispensable process during tumor progression and metastasis. Blockage of tumor angiogenesis by targeting and inhibiting endothelial cell has emerged as novel safe and efficacious method to control many advanced malignant diseases. Numerous clinical studies are currently testing new antiangiogenic drugs which target and inhibit endothelial cell markers, receptors or molecules which transmit receptor-mediated signals, therefore inhibiting endothelial cell proliferation, migration and vascular tube formation. Many of these drugs are now widely used in clinical settings as first- or second-line chemotherapy in advanced malignant conditions. So far, these therapeutic approaches gave modest, yet encouraging clinical improvements, prolonging survival and improving functional capacity and quality of life for many terminally ill patients. Here we present the most commonly used endothelial cell markers along with their applicability in contemporary clinical practice.