Vandetanib is a small-molecule inhibitor of vascular endothelial growth factor receptor (VEGFR), epidermal growth factor receptor (EGFR), and RET tyrosine kinases that has demonstrated clinical benefits in patients with medullary thyroid cancer (MTC). By identifying patients who are in greatest need of therapy, the risks of vandetanib can be balanced against the potential benefits in patients for whom there had been no effective therapy until now. This review discusses the development of vandetanib in patients with MTC and the benefits and risks in this patient population.