The use of inhibitors of vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor 2 (VEGFR2) signaling for the treatment of cancer has increased over the last decade. This signaling pathway plays a fundamental role in angiogenesis and also in kidney physiology. The emergence of anti-angiogenic therapies has led to adverse nephrotoxic effects, despite improving the outcomes of patients. In this review, we will present the different anti-angiogenic therapies targeting the VEGFR pathway in association with the incidence of renal manifestations during their use. In addition, we will discuss, in detail, the pathophysiological mechanisms of frequent renal diseases such as hypertension, proteinuria, renal dysfunction, and electrolyte disorders. Finally, we will outline the cellular damage described following these therapies.