Stimulation by recombinant human thyroid-stimulating hormone (rhTSH) has gained wide acceptance as an alternative to thyroid hormone withdrawal in the management of patients with differentiated thyroid cancer. RhTSH has the advantage to avoid both the clinical consequences of hypothyroidism, with a positive impact on quality of life and work productivity, and the risk of cancer growth due to the long-lasting endogenous thyrotropin stimulation. RhTSH is a heterodimeric glycoprotein produced by recombinant DNA technology that has the ability to stimulate thyroglobulin production and radioiodine uptake by thyroid cells. RhTSH is now widely used in the follow-up of thyroid cancer patients in order to improve sensitivity of thyroglobulin (Tg) measurement as well as in preparation of (131)I diagnostic whole-body scan. Although initially approved only for diagnostic purposes, rhTSH has been now approved both in Europe and in the United States for remnant ablation in low-risk patients. As far as residual or metastatic cancer treatment, rhTSH has been initially used on a compassionate need basis for elderly and frailer patients and for patients in whom the withdrawal of thyroid hormone was medically contraindicated. Nowadays, there is a trend for widening the use of rhTSH in therapy, in order to avoid hypothyroidism and the concern about the effect of prolonged endogenous thyroid-stimulating hormone stimulation on cancerous cells. Unfortunately, the studies which address the efficacy of rhTSH in cancer treatment are still scarce and the opportunity of its clinical application remains controversial. In addition, rhTSH has been shown to improve the accuracy of [(18)F]-2-fluoro-deoxy-D-glucose positron emission tomography to detect non-functioning thyroid cancer. Although all studies agree on that rhTSH is much better tolerated from the clinical point of view than thyroid hormone withdrawal, there is some controversy about its comparative ability to raise Tg levels and concentrate radioiodine in cancerous thyroid cells. The aim of this paper is to review the performances of rhTSH as compared to hypothyroidism, considering Tg stimulation and diagnostic whole-body scan sensitivity during follow-up, and its effectiveness for normal remnant ablation and for therapy of metastatic disease.