Prognostic factors for the survival of patients undergoing immunotherapy for metastatic renal cell carcinoma (RCC) were first published in 1999 by Motzer et al. Since then several modifications of the prognostic model have been published. Even if not validated for targeted therapies stratification of RCC patients based on the prognostic factors provided the basis for recent clinical trials investigating the efficacy of sorafenib, sunitinib, temsirolimus, or bevacizumab/interferon. In order to compare the results of the trials and to generate treatment algorithms one has to carefully examine the prognostic factors used in the trials. The present article reviews the development of the prognostic models and their use in recent clinical trials. Furthermore, a reasonable algorithm for the treatment of patients with metastatic RCC is presented.