Thyroid-stimulating hormone (TSH) is crucial for the modulation of thyroid hormone release and growth of the thyroid gland. The hypothalamic-pituitary axis regulates TSH release. The hypothalamus releases thyroid-releasing hormone (TRH), which stimulates thyrotrophs of the anterior pituitary to secrete TSH. TSH is released by the anterior pituitary and stimulates the thyroid follicular cells to release thyroxine, T4 (80%) and triiodothyronine, or T3 (20%). When T4 is released into circulation, it can be converted to T3 through the process of de-iodination. T4 and T3 can then exert negative feedback on TSH levels with high levels of T3/T4 decreasing TSH and low levels of T3/T4 increasing TSH levels from the anterior pituitary. In this review, we discuss the physiology, biochemistry, and clinical relevance of TSH.