Routine treatment of thyroid cancer (TC) includes long-term suppression of TSH. The necessity of this treatment in low- and intermediate-risk patients as well as the extent of TSH suppression is currently under discussion. A literature search was performed to illustrate the role of TSH in extrathyroidal cells and to identify potential reasons for different effects of exogenously suppressed and endogenously low TSH levels. Although adverse effects of subnormal and supranormal TSH blood levels on heart and brain have not been consistently found, studies show a clear negative effect of suppressed TSH levels on bone mineral density. Experimental data also support an important role of TSH in the immune system. The ability of levothyroxine (l-T4) to regulate TSH levels and triiodothyronine levels in a physiological manner is limited. Reduction of circadian changes in TSH levels, decrease of thyroid hormone-binding proteins, prevention of potential compensatory increases of TSH levels (e.g., in old age), and unresponsiveness of TSH-producing cells to TRH on l-T4 treatment might cause adverse effects of suppressed TSH levels. In view of the adverse effects of aggressive TSH suppression, achieving the suggested levels of TSH between 0.9 and 1 mU/l in the treatment of low-to-intermediate risk TC patients appears justified.