Thyroid-associated ophthalmopathy is a complex disease whose pathogenesis is thought to be autoimmune. Evidence has accumulated to implicate lymphocytes, antibodies, and cytokines targeting the orbital tissues whose structural and functional characteristics are unique. Epitope sharing between the orbit and the thyroid is the likely explanation for the close association of ophthalmopathy with autoimmune thyroid disease. Environmental and other nonautoimmune factors are identified that also play a part in the initiation or perpetuation of the disease process.