Papillary and follicular cancers of thyroid are the most common varieties of differentiated thyroid cancers exhibiting excellent long-term prognosis when carefully managed. Being a slow-growing malignancy, guidelines exist on the staging, preoperative risk stratification, and management of these cancers to increase the overall survival of these patients. Radioactive iodine has a central role in differentiated thyroid malignancies. It has the same physical properties as stable iodine, thus both normal and malignant thyrocytes cannot differentiate radioactive from stable iodine. Differentiated thyroid carcinoma (DTC) cells concentrate cytocidal amounts of Iodine -131 (131 I) by trapping (the function of the sodium iodine symporter, or NIS) and organifying the iodide ion to produce levothyroxine and triiodothyronine. We shall discuss the role of radioiodine in the management and followup of DTC patients.