Vascular endothelial growth factor (VEGF) is an endogenous polypeptide that modulates angiogenesis in normal physiological conditions as well as in cancer. During angiogenesis, VEGF interacts with several other angiogenic factors, playing an important role in cell proliferation, differentiation, migration, cell survival, nitric oxide (NO) production, release of other growth factors and sympathetic innervation. Based on these mechanisms of action, several anti-VEGF drugs have been developed for cancer treatment. This review discusses the physiology and interactions of VEGF, its mechanisms of action and role in modulating vascular homeostasis. It also discusses the adverse cardiovascular effects of recently developed anti-VEGF drugs for the treatment of various types of cancer. A critical appraisal of the human studies on these drugs is provided. Furthermore, putative mechanisms for the onset of hypertension, the most common adverse cardiovascular effect, are discussed.