The past 5 years were marked by fundamental changes in the systemic therapy of metastatic renal cell carcinoma. Up to the end of the last decade cytokine-based chemotherapy was the only, even if only moderately effective systemic therapy for metastatic renal cell carcinoma. Currently there are five new approved drug releases of so-called targeted substances, which function on a molecular based therapeutic mechanism. Sunitinib (Sutent) and sorafenib (Nexavar) as multikinase inhibitors, everolimus (Afinitor) and temsirolimus (Torisel) as mTOR inhibitors, and bevacizumab as an antibody against VEGF in combination with interferon-alpha (IFN-alpha). The following article will give an overview of the currently available substances and critically discuss therapy plans and future trends.