Medullary thyroid carcinoma (MTC) is a neuroendocrine malignancy that occurs in hereditary (25%) and sporadic (75%) clinical settings. MTC is present in all patients with the multiple endocrine neoplasia type 2 (MEN 2) syndromes. MTCs produce calcitonin, measurement of which indicates the presence of tumor in at-risk individuals and the effectiveness of therapy in treated patients. Surgery is the mainstay of therapy for primary and recurrent disease. Routine serial postoperative measurement of calcitonin levels should be done. Patients with elevated calcitonin levels should have imaging by computed tomography scan, magnetic resonance imaging, and/or fluorodeoxyglucose positron emission tomography to identify sites of recurrence and metastasis. The role of radiation therapy is not well defined. There is no effective systemic therapy for MTC at present. Activating mutations in a tyrosine kinase receptor gene are present in the majority of MTCs, and experience with tyrosine kinase inhibitors and other agents in the setting of clinical trials is critical for the identification of effective systemic treatment.