Radioactive iodine (RAI) in the form of 131I has been used to treat thyroid cancer since 1946. RAI is used after thyroidectomy to ablate the residual normal thyroid remnant, as adjuvant therapy, and to treat thyroid cancer metastases. Although the benefits of using RAI in low-risk patients with thyroid cancer are debated, it is frequently used in most patients with thyroid cancer and is clearly associated with acute and long-term risks and side effects. Acute risks associated with RAI therapy include nausea and vomiting, ageusia (loss of taste), salivary gland swelling, and pain. Longer-term complications include recurrent sialoadenitis associated with xerostomia, mouth pain, dental caries, pulmonary fibrosis, nasolacrimal outflow obstruction, and second primary malignancies. This article summarizes the common complications of RAI and methods to prevent and manage these complications.