Metastatic or recurrent renal cell carcinoma (RCC) carries a poor prognosis and long term survival is rare. However, many small RCCs that are incidentally discovered have an indolent course even without treatment. The variability in clinical outcome is a reflection of the underlying tumor biology. Currently, clinical variables such as tumor stage and histologic grade are widely accepted surrogates for tumor-specific cellular and molecular processes. Ongoing advances in genomic and proteomic technologies have produced an expanding list of molecular markers for predicting prognosis. We review expression array studies evaluating molecular signatures for predicting prognosis in patients with RCC and describe specific prognostic markers that have been validated in at least 50 cases of RCC.