For over 200 years, the relationships between neuroendocrine systems and mental illness have been studied. Research has focused in substantial part on mood disorders and thyroid axis function. This review presents a brief examination of the history and the progress in this area of investigation. Consideration is given to mood states in thyroid disorders, as well as to thyroid function in mood disorders. Thyroid hormones, usually in conjunction with standard medications, can be used to treat both manic and depressed phases of mood disorders. The review with a presentation of some of the many issues that merit further investigation.