Sunitinib is an oral multikinase inhibitor that blocks the vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR) alpha and beta, c-kit, and other receptors. These attributes have proven to be efficacious in the treatment of metastatic renal cell carcinoma (RCC), unresectable gastrointestinal stromal tumors (GIST), and well-differentiated advanced pancreatic neuroendocrine tumors (PNET). Though activity has been reported in other tumor types, phase III trials have not yet demonstrated improved survival outcomes in these cancers. Most side effects including hypertension, hand-foot syndrome, and diarrhea are generally well manageable. This review will detail the preclinical data leading up to the results of the pivotal phase III clinical trials that have led to the widespread use of sunitinib in advanced RCC, GIST, and PNET.