The etiology of Graves' orbitopathy (GO) remains enigmatic. Optimal therapeutic choices for the hyperthyroidism associated with Graves' disease (GD) in the presence of GO remain controversial. Whether antithyroid drugs (ATDs), radioiodine (RAI), or thyroidectomy should be favored in such patients remains debated. Pre-therapy variables such as ethnicity, sex, age, thyroid function, level of TSH-receptor antibodies and smoking behavior influence response to therapy. Among the most important management goals are restoring euthyroidism and abstaining from smoking. On average, ATDs and thyroidectomy - independent of extent - do not influence the natural course of GO. RAI can cause de novo development or progression of GO, which is largely preventable with oral steroid prophylaxis. In patients with mild GO, the thyroid treatment is largely independent of GO. Moderate to severe GO should be treated promptly. Deciding whether, in the latter, GD is better treated with ATDs, RAI, or surgery, is based more on expert opinion than on evidence. It is clear that in the individual patient a number of factors, not addressed in any trial, influence the final choice of therapy for GD, including concern of developing or negatively affecting pre-existing GO. Evidently, there is room for improving therapy of GO. Progress using novel drugs such as rituximab, which might potentially influence positively both GD and GO, are impatiently awaited.