The medical treatment of renal-cell carcinoma, and of its most frequent subtype, clear cell renal-cell carcinoma, has recently been drastically changed by the emergence of targeted therapies. The development of these drugs has been made possible by more precise knowledge of molecular mechanisms involved in the carcinogenesis of these tumors. We present in this article the molecular pathways linked to targeted therapies for clear cell renal-cell carcinoma: VHL/HIF/VEHF and PI3K/AkT/mTOR pathways. We also describe succinctly the EGFR pathways, and the molecular mechanisms involved in other histological subtypes. Then, we briefly describe how these targeted therapies work. We finally discuss how biology could improve the use of these therapies, by developing new prognostic factors, and predictive factors of response to treatment.