The clinical benefits of recombinant human thyroid-stimulating hormone (rhTSH; Thyrogen^®, Genzyme Corp., Cambridge, MA, USA) are well established as an alternative stimulation procedure to thyroid hormone withdrawal in the follow-up of thyroid cancer patients. rhTSH has the advantage to avoid both hypothyroidism, with a major impact on the quality of life, and the side effects on tumor growth related to the long-lasting TSH increase. More recently, alternative uses have been proposed, including treatment of nodular goiter, TSH stimulation to enhance PET scanning and chemotherapy treatment, and differential diagnosis of congenital hypothyroidism. In benign thyroid diseases, rhTSH administration increases thyroid uptake resulting in a more homogeneous distribution of the tracer, and allows to reduce the dose of ¹³¹I maintaining the same effects on thyroid shrinkage. Moreover, rTSH stimulation improves the detectability of occult thyroid metastases with FDG-PET, and promising results have been obtained in the response rate of poorly differentiated thyroid cancer submitted to chemotherapy after rhTSH stimulation. Finally, rhTSH testing has been proved to be safe and to lead, in association with ultrasound, to the differential diagnosis of congenital hypothyroidism during L-thyroxine, allowing the appropriate clinical/genetic management of the disease and thus representing a valuable alternative to L-thyroxine withdrawal.