The recent development of agents targeting VHL-related growth factors as therapy for metastatic renal cell carcinoma has generated a revolution in the management of these patients, with a clear improvement of survival. However, there are still many questions related to these antiangiogenic agents and upcoming studies are strongly warranted to provide answers. The controversy is ongoing regarding several specific questions as the use of antiangiogenic treatments remains a moot point in certain cases. Notably, the role for radical nephrectomy in metastatic cases, the interest of adjuvant treatment in high-risk recurrence cases, the place for neoadjuvant treatment in locally advanced renal cell carcinoma, the choice of the best agent at first-line treatment, the various therapeutic options and their consequences on the quality of life and the potential contribution of dynamic imaging to assess antiangiogenic treatment's efficiency.