Vascular endothelial growth factor (VEGF), a disulfide-linked homodimer, also known as VEGF-A, belongs to the platelet-derived growth factor superfamily. VEGF is secreted by vascular smooth muscle cells upon hypoxic conditions and promotes angiogenesis and vasculogenesis, vascular permeability, and inhibition of apoptosis, through the binding to two cell surface receptors, VEGFR1 (Flt-1) and VEGFR2 (KDR/Flk-1), and other co-receptors, which are expressed mainly on endothelial cells and immune cells. VEGFR2 mediates almost all observed endothelial responses to VEGF, while Neuropilin-1 acts as co-receptor for the VEGF 165 aa isoform and enhances its binding to VEGFR2 and its biological activity. The VEGF/VEGFR system supports initiation of inflammation, inducing migration of monocytes and macrophages, but also acts on neurons and kidney epithelial cells. Moreover, VEGF contributes to tumor growth and metastasis formation, and is crucial during embryonic development and wound healing. Alteration in VEGF/VEGFR pathways have been associated with diseases, such as cancer, age-related macular degeneration, preeclampsia, rheumatoid arthritis, and neuronal disorders, such as amyotrophic lateral sclerosis. Several isoforms are generated as a result of alternative splicing, including the soluble isoforms VEGF 121 aa and VEGF 165 aa in human, and VEGF 164 aa isoform in mouse.