Although the focus in the last decades has been on the overdiagnosis of incidentally detected thyroid carcinomas in early stages, the other extreme of the disease is represented by locally advanced tumors with the invasion of neighboring structures. These are infrequent tumors, but they have a high complexity and a poor prognosis. In the absence of effective therapies allowing preoperative tumor reduction, in order to achieve a more restricted surgery, treatment was limited to aggressive surgery with resection of the aerodigestive tract and major vascular structures or palliative treatment. However, due to the increased knowledge of tumor biology and the results that tyrosine kinase inhibitors have achieved in the treatment of radioactive iodine-refractory tumors, neoadjuvant therapy with a curative intent has emerged as a reality to be taken into account when dealing with these patients. This paper presents a narrative review of the current scientific evidence regarding neoadjuvant treatment in locally advanced thyroid cancer.