Central hypothyroidism is defined as low circulating free thyroxine (free T4) with inappropriately low circulating thyrotropin (TSH), in context of a hypothalamic pituitary pathology. Rare cases of idiopathic central hypothyroidism caused by a functional defect may occur, and the condition is often overlooked due to difficulty in achieving the correct diagnosis, sparse symptomatology of the condition and a high risk of misinterpretion of the biochemical changes in central hypothyroidism. Central hypothyroidism is mainly seen in patients with hypothalamic–pituitary pathology due to one of many possible aetiologies, where other hormone deficiencies often co-exist, and both the presence of other deficiencies and their replacement have a strong influence on the measurement of the thyroid-related hormones and thereby interpretation of the thyroid function variables in relation to the clinical impact of thyroid hormone substitution therapy. Conversely, lack of thyroid hormone has a similar strong influence on the interpretation of other pituitary hormone axes, as well as their replacement. Undertreating patients with central hypothyroidism may have serious metabolic consequences with a potentially increased risk of cardiovascular morbidity. The present review thus aims at describing central hypothyroidism, by an overview of interactions of hypothyroidism with other pituitary hormones, diagnosing/testing for central hypothyroidism, and focusing on consequences of undertreatment. Finally, it is mentioned how to deal with new diagnostic settings with lower a priori likelihood of hypopituitarism, particularly in view of the importance of stringent diagnostic testing in order to avoid overdiagnosing central hypothyroidism.