For patients undergoing radioiodine therapy of differentiated thyroid carcinoma (DTC), TSH stimulation prior to radioiodine therapy (RIT) can be achieved using thyroid hormone withdrawal (THW) or administration of recombinant human TSH (rhTSH). As THW can lead to nausea, headaches, vomiting, fatigue and dizziness secondary to transient acute hypothyroidism, rhTSH could be a good alternative. rhTSH has been administered in patients in order to stimulate TSH for RIT since 2005. According to the Martinique criteria formulated by the leading professional societies involved in care of patients with DTC, rhTSH can be applied in three settings: for remnant ablation, adjuvant treatment and treatment of known disease. Numerous studies have investigated the effects of rhTSH as a method of TSH stimulation on the thyroid cell, the systemic effects, biokinetics and clinical outcomes, however no consensus has been reached about many aspects of its potential use. rhTSH is able to stimulate sufficient TSH-levels (>30 mIU/L) and is hypothesized to decrease risks of tumor cell proliferation. As rhTSH-use avoids the transiently-impaired renal function associated with THW, radioiodine excretion is faster with the former, leading to to a lower iodine-131(I-131) uptake and a difference in fractional remnant uptake, effective half-life, mean residence time, and dose to the blood. Differences between rhTSH and THW were observed in radioiodine genotoxic effects and endothelial-dependent vasodilation and inflammation. For thyroid remnant ablation, THW and rhTSH lead to similar remnant ablation rates. For adjuvant therapy and treatment of known disease, insufficient trials have been conducted and future prospective studies are recommended.