With the recent advances in targeted therapies, biomarkers in renal cell carcinoma (RCC) continue to be developed. Historically, information regarding prognosis has come from clinicopathologic variables, however in recent years much research has focused on the molecular basis of renal cell cancer. The discovery of reliable biomarkers in RCC could have an important impact on diagnosis, prognosis, and prediction of therapeutic benefit. To date, most biomarker research has centered on byproducts of the von Hippel-Lindau (VHL) pathway including VHL mutations, vascular endothelial growth factor (ligands and receptors), hypoxia-inducible factor, and carbonic anhydrase IX. This review examines these potential biomarkers, biomarker prognostic models, and molecular expression profiles in the field of renal cell carcinoma.