Angiogenesis, the formation of new blood vessels from preexisting ones, is a central process during normal development and during pathological repair. Vascular endothelial growth factor‐A (VEGF‐A) can stimulate both physiological and pathological angiogensis. VEGF‐A is a ligand for the two receptor tyrosine kinases VEGFR‐1 (Flt‐1) and VEGFR‐2 (KDR/Flk‐1). Most biological functions of VEGF‐A are mediated via VEGFR‐2, whereas the role of VEGFR‐1 is largely unknown. Activation of mitogenactivated kinase, stress‐activated kinase, protein kinase C, and the Akt pathway are implicated in VEGF‐A‐dependent endothelial function, including cell survival, proliferation, generation of nitric oxide, and the induction of angiogenesis. Induction of metalloproteinases, activation of focal adhesion kinase and of PI3‐kinase are implicated in VEGF‐A‐induced endothelial cell migration. The important role of nitric oxide as a mediator of endothelial function in vivo links the receptor signaling network to other biological effects.