Medullary thyroid carcinoma (MTC) is a neuroendocrine malignancy of the thyroid C cells. Metastatic spread commonly occurs to cervical and mediastinal lymph nodes. MTC cells do not concentrate radioactive iodine and are not sensitive to hormonal manipulation. Surgery is currently the only therapy that can reliably lead to cure, reduction in tumor burden, or effective palliation. In patients with hereditary MTC, central lymph node dissection should be considered in preventative operations if the calcitonin level is elevated. Systematic surgical removal of at-risk or involved lymph node basins (compartmental dissection) should be performed in all patients with palpable primary tumors and recurrent disease. A “berry-picking” approach is discouraged. Although data are limited, standard chemotherapy and radiation therapy have not been shown to be effective in the treatment of MTC. Newer targeted drug therapies are promising and are being examined in therapeutic clinical trials.