Sunitinib is an orally available, multitargeted tyrosine kinase inhibitor licensed for the treatment of metastatic renal cell carcinoma. This article is an in-depth review of the mechanism of action of sunitinib, rationale for dose and schedule, toxicity and clinical efficacy. Other targeted therapies and treatment combinations for renal cell carcinoma are discussed. The use of sunitinib for other indications, biomarkers of response and future directions are explored.