Advances in the measurement of thyroid gland function have often introduced new concepts which led to the development of analogous diagnostic procedures in other areas of clinical endocrinology. The qualitative clinical assessment of patients with hyperthyroidism and hypothyroidism was first buttressed by quantification of target tissue responses to thyroid hormone with the basal metabolic rate (BMR) (Magnus-Levy, 1895) and later the Achilles tendon reflex time (Lawson, 1958). Thyroid hormones were initially measured indirectly by bioassay in the tadpole metamorphosis test, and subsequently by chemical analysis with protein-bound iodine (PBI) and butanol-extractable iodine (BEl) determinations (Barker, 1948). Assessment of thyroid gland function was among the earliest uses of radionuclide agents (Cassen, 1975). The competitive protein-binding assay was first applied to hormonal diagnostic studies in the measurement of circulating thyroxine concentration by the Murphy-Pattee method (Murphy and Pattee, 1964), and subsequently by specific L-thyroxine immunoassay (Chopra et al, 1971). Over the past two decades, many additional techniques have been developed for the determination of serum total and free iodothyronine concentrations, the assessment of in vivo feedback on hypothalamicpituitary control, the detection of circulating markers for specific thyroidal diseases, and the quantification of peripheral responses to thyroid hormones in target tissues. These tools now permit the recognition of subtle thyroid dysfunction which previously escaped laboratory detection, the more accurate differential diagnosis of the underlying disease processes, and the description of entirely novel thyroid disorders, e.g., thyroid hormone resistance. At the same time, this proliferation of thyroid function tests has created confusion concerning their terminology, methodology, and interpretation. In particular, a challenge is posed by the patient with multiple thyroid laboratory test abnormalities attributable entirely to non-thyroidal illness and/or pharmacological agents.