Radionuclide therapy using iodine-131 is widely employed in the work-up of differentiated thyroid carcinoma. After a brief introduction on physical and dosimetry characteristics of radioactive iodine, this paper suggests state of the arts protocol for the ablation of thyroid remnants and for the treatment of metastatic disease. Diagnostic applications of Nuclear Medicine in these tumors are critically evaluated as well, from the use of iodine-131 whole-body scan to 18F-FDG PET and other new diagnostic tools. Finally, a brief description of new radionuclide treatments is reported.