Renal cell carcinoma (RCC) and its most frequent subtype, the clear cell hystology type, has shown resistance to chemotherapy and radiotherapy treatment when disease was already spread in patients. Recently, a huge advance in the molecular biology of this tumor has been performed. This fact allowed a deeper and better knowledge of the disease and the development of new drugs that work against the growth factors involved in tumor origin. In this review article it is summarized the molecular milestones that are involved in the development of clear cell renal cell carcinomas.