OBJECTIVE Vandetanib is a small molecule tyrosine kinase inhibitor that has been recently approved as an 'orphan drug' for the treatment of patients with unresectable, locally advanced, or metastatic medullary thyroid cancer (MTC). RESULTS MTC is a neuroendocrine malignancy frequently associated with mutations to the RET proto-oncogene. Vandetanib selectively targets RET, vascular endothelial growth factor receptor-2, and epidermal growth factor receptor dependent signaling. Vandetanib has been shown to improve progression-free survival in patients with advanced MTC. In general, vandetanib is well tolerated, but QTc prolongation remains a potential concern demanding careful patient selection and monitoring. CONCLUSIONS Vandetanib has emerged as one of the more promising small molecule tyrosinse kinase inhibitors, providing durable rates of disease stabilization, with an acceptable adverse event profile in patients with advanced MTC.