In recent years, there have been increased incidences of metastatic renal cell carcinoma (RCC), which is refractory to conventional chemotherapy. Owing to the insensitivity to traditional therapy, targeted therapy becomes a possible alternative strategy. Over the past decade, the development of targeted treatments for metastatic RCC has advanced considerably. Several studies have shown that the vascular endothelial growth factor pathway is an important mediator for the occurrence and development of RCC, and tyrosine kinase inhibitors (TKIs) that target vascular endothelial growth factor receptors (VEGFRs) have been considered optimal therapeutic options for RCC. Six small molecules that inhibit VEGFR1/2/3, namely, sunitinib, sorafenib, axitinib, pazopanib, cabozantinib, and lenvatinib, have been approved by the Food and Drug Administration (FDA) for the treatment of RCC. Additionally, clinical trials assessing seven TKIs that target VEGFRs are currently in progress. To some extent, these drugs improve quality of life and prolong the survival of patients. This paper presents a review of the systemic targeted therapies against VEGFRs that have been approved so far or are undergoing trials as treatments for RCC. (C) 2020 Elsevier Masson SAS. All rights reserved.