In the preceding two decades, several milestones have been reached in the management of patients with metastatic renal cell carcinoma (mRCC), including the development of novel targeted agents paralleling an increased understanding of the molecular biology of this disease process. Recently, a renewed enthusiasm for immunotherapy in the form of immune checkpoint blockade has resulted in significant strides in the treatment of mRCC. Despite these advances, treatment remains challenging for clinicians, and only modest survival benefits are observed with current treatment paradigms. The risk-stratification tools and investigated predictive and prognostic biomarkers in patients with mRCC are detailed in this review.