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Although multikinase inhibitors are established therapies in advanced thyroid cancers, treatment-related adverse events can lead to dose reductions and discontinuations, thereby limiting the effectiveness of these treatments. Gene‐specific treatments have emerged as new standard-of-care therapies, and continue to demonstrate efficacy and improved tolerability, although genotyping is needed to identify patients that would benefit from these therapies and more education is needed in regard to the optimal use of these novel agents. Additionally, the emergence of acquired resistance has become a new problem in the field.