Recent advances in genetics and oncology have led to development of a wide array of molecular therapeutics in the management of patients with metastatic renal cell carcinoma. These drugs have revolutionized the treatment of advanced disease by significantly improving patient outcomes. State-of-the-art cross-sectional imaging techniques play a seminal role in the evaluation of treatment response by providing reproducible, objective data, thereby permitting accurate quantification of tumor burden. Evolving functional imaging techniques such as perfusion and diffusion studies continue to advance the technology beyond assessing changes in tumor size and morphology.