Alterations in thyroid function tests are common in non-thyroidal illness. There remains a significant debate as to whether these alterations contribute to morbidity and mortality. Recent data have highlighted the heterogeneity and natural history of altered thyroid function in non-thyroidal illness; particularly in relation to critical illness. Moreover, the biological mediators of these changes are becoming clearer. This presentation will review the physiology and pathophysiology of thyroid function in non-thyroidal illness and provide a framework for understanding both the processes involved and the impact on outcome.