In the last 5 years the paradigms for the treatment of metastatic renal cell cancer have fundamentally changed. Until 2005 systemic therapy was limited to the immunomodulating cytokines interferon-alfa and interleukin-2, in recent years, however, tyrosine kinase inhibitors, mTor inhibitors and monoclonal antibodies have been established for this therapeutic situation. Without validated predictive biomarkers it is currently not possible to select patients who are likely to benefit from a certain therapy. Therefore, most current guidelines stratify the patients into risk groups according to the MSKCC risk score. The resulting treatment algorithm for first-line therapy is limited to these new drugs within all risk groups. Since approval for more tyrosine kinase inhibitors and mTOR inhibitors is currently awaited, the number of treatment options will expand further in the near future. The present paper reviews the present study data and aims to provide practical advice for the treatment of patients suffering from metastatic renal cell cancer.