Systemic treatment of metastatic renal cell carcinoma has changed fundamentally in recent years. So-called targeted therapy gives patients with incurable renal cell cancer the chance of prolonged survival with acceptable quality of life and manageable side effects. Several tyrosine kinase inhibitors and mTOR inhibitors have been evaluated in various clinical settings within prospective trials. Therefore, recent medical guidelines are able to give recommendations for the management of advanced renal cell carcinoma in daily practice. The optimal therapeutic sequence of the available substances has not been defined until now; however recent data recommend the use of a tyrosine kinase inhibitor as the first line treatment. Besides standard treatment, new approaches are currently being evaluated in clinical trials.