Objectives. Invasion of differentiated thyroid cancer (DTC) into surrounding structures can lead to morbid procedures such as laryngectomy and tracheal resection. In these patients, there is a potential role for neoadjuvant therapy. Methods. We identified three studies involving the treatment of DTC with neoadjuvant chemotherapy: two from Slovenia and one from Japan. Results. These studies demonstrate that in selected situations, neoadjuvant chemotherapy can have a good response and allow for a more complete surgical resection, the treatment of DTC. Additionally, the SELECT trial shows that the targeted therapy lenvatinib is effective in the treatment of DTC and could be useful as neoadjuvant therapy for this disease due to its short time to response. Pazopanib has also demonstrated promise in phase II data. Conclusions. Thus, chemotherapy in the neoadjuvant setting could possibly be useful for managing advanced DTC. Additionally, some of the new tyrosine kinase inhibitors (TKIs) hold promise for use in the neoadjuvant setting in DTC.