Abstract Active moderate-to-severe TAO is a disease, the treatment of which requires a multidisciplinary team, an individualized approach and strict follow-up, yet it is often suboptimal. Recent knowledge about the pathogenesis of the disease and the randomized controlled trials conducted in recent years made it possible to use new therapeutic combinations and biological agents. The currently recommended first-line therapy for active moderate-to-severe TAO is the combination of intravenous glucocorticoids (GCs) in moderate doses and mycophenolate or, in more severe cases, a high-dose GC treatment alone. There are several options for second-choice therapy, if needed: a new course with GCs, combination of orbital radiotherapy and GCs (preferably intravenous), cyclosporine and oral GCs, azathioprine and oral GCs, rituximab, tocilizumab or teprotumumab. The clinical manifestations of TAO should also be considered when choosing second-line treatment. Thus, for example, teprotumumab best affects diplopia, orbital radiotherapy – visual disturbances and diplopia, while intravenous GCs, mycophenolate, cyclosporine, rituximab and tocilizumab – the inflammatory manifestations of TAO. However, the question of the availability of the new drugs in routine clinical practice remains unsolved.