Publisher Summary This chapter discusses the properties of thyroid hormones (TH) and the thyroid cascade and considers the problems inherent in evaluating fish thyroidal responses. The chapter focuses on possible mechanisms of fish thyroid disruption. Vertebrate thyroid system can be influenced by environmental chemicals identified as ecotoxicants (xenobiotics). Analysis of the thyroid cascade and the effects of potential ecotoxicants involve many steps from acquisition of environmentally scarce iodide to TH binding to target receptors and expression of physiologic responses: (1) iodide acquisition, (2) TH biosynthesis and storage, (3) TH secretion, (4) control of thyroid secretion, (5) TH in the circulation and tissues, (6) TH metabolism, (7) TH degradation rate (DR), and (8) TH actions. One underlying problem in evaluating fish thyroidal responses is the failure to distinguish direct and indirect thyroid responses.