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The landscape of treatment options for radioactive iodine refractory thyroid cancer is rapidly changing. While there are no curative options in this setting, tyrosine kinase inhibitors (TKIs) have revolutionized the management of radioiodine refractory disease to help delay progression of metastatic and life-threatening disease. Ongoing development of more selective targeted inhibitors will certainly improve medication tolerability and tumor specificity. In this review, we discuss the epidemiology of radioactive iodine refractory thyroi