OBJECTIVE Radioiodine ((131)I) is considered an effective and low-risk therapeutic radionuclide for differentiated thyroid carcinoma (DTC); however, dilemmas exist in the optimization of indications, pre-treatment thyroid stimulating hormone (TSH) stimulation, dose decision, as well as in the treatment of (131)I-refractory disease. Refined strategies on (131)I treatment for DTC based on late evidence and novel insights are greatly needed. CONCLUSIONS The indications of (131)I ablation continue to be refined with a better understanding of the risks and benefits. For pre-treatment TSH stimulation, recombinant human thyrotropin presents a better choice as it improves the quality of life, but is indicated only for ablation of the thyroid remnant and follow-up. Decreased doses of (131)I seem to be more appropriate in patients without gross residual disease or metastases, but maximal doses are suggested in patients with advanced disease. Imaging procedures contributing to decision-making for patients with advanced DTC also continue to be modified. As for the (131)I-refractory disease, there is a trend to increase (131)I uptake and retention by using additional therapeutic agents like kinase inhibitors with encouraging results.