The ability to noninvasively discriminate the most common types of renal cell carcinoma (RCC) based on their magnetic resonance imaging (MRI) appearances or their magnetic resonance phenotypes is achievable. Intracellular lipids, a histologic characteristic of the clear cell RCC, can be identified on chemical shift MRI. Intratumoral hemosiderin deposition, as observed histologically with papillary RCC, correlates to the low signal intensity on T2-weighted images. In addition to morphologic imaging features, the different subtypes of RCC have distinct patterns of enhancement on dynamic contrast-enhanced MRI. Clear cell tumors demonstrate much greater enhancement than papillary and chromophobe RCCs during the corticomedullary and nephrographic phases. The MRI technique arterial spin labeling (ASL) uses magnetic fields to label the water protons in arterial blood and measures blood flow into tissue; quantitative images of blood flow can be generated without exogenous contrast media. Multiple measurements of tumor perfusion may be repeated before and after a physiologic or drug challenge (ie, antiangiogenic therapy). In RCC xenografts and in patients with metastatic RCC, ASL MRI assessments can be used to monitor blood flow changes in response to antiangiogenic therapies. High blood flow on ASL MRI in RCC xenografts correlates with viable tumor at histopathologic analysis, whereas zones of absent or diminished signal correspond to necrosis. ASL MRI has the potential to serve as a biomarker for patients with metastatic RCC by offering a noninvasive measure of tumor blood flow changes accompanying antiangiogenic therapy. Cancer 2009;115(10 suppl):2334-45. © 2009 American Cancer Society.