The medical treatment of Graves' orbitopathy (GO) is usually reserved to 
moderate to severe disease. Steroids have been widely employed and possess 
anti-inflammatory activity, but about 20-30% of patients are not responsive and 
about 20% present with disease recurrence. Immunosuppressive therapy alternative 
to corticosteroids may target the different antigens involved in pathogenic 
mechanisms of GO. Some have already been employed in clinical studies and showed 
interesting results, although the lack of randomized and controlled trials 
suggests caution for their use in clinical practice. Potential targets for 
therapy in GO are the TSH receptor and the IGF-1 receptor on the fibroblasts, 
inflammatory cytokines, B and T cells. Most promising results are obtained by 
interacting with the PIK3/mTORC1 signaling cascades for adipogenesis and the 
anti-IGF-1R with the monoclonal antibody teprotumumab. A recent open study has 
shown that tocilizumab, an anti-sIL-6R antibody, inactivates GO. Consistent 
reports on the efficacy of rituximab have recently been challenged by randomized 
controlled trials. Clinical practice will greatly benefit from the use of 
disease modifying agents in GO, as compared to steroids, currently standard 
treatment for GO. Among these, rituximab may be useful, especially in patients 
resistant to steroid or with contraindications to steroids. However, larger 
randomized controlled trials are needed for definitive data on the potential 
disease-modifying role of rituximab in GO. Direct targeting of the orbital 
fibroblast via immunosuppression or nonimmunosuppressive drugs is emerging as a 
promising alternative.