Steroids act via suppression of the immune system in two different ways: a genomic and a non-genomic pathway. While the non-genomic pathway appears to be responsible for the quick effects only a few minutes after application, the genomic pathway determines the long-time effects. Since decades, systemic steroids have been applied in the management of severe Graves orbitopathy (GO). In GO, steroids effectively modulate both the effector cells as well as the orbital targets cells, i.e. fibroblasts and pre-adipocytes. They inhibit the release of inflammatory mediators i.e. cytokines and prostaglandins. Also, systemic steroids significantly reduce the titer of the disease relevant thyroid-stimulating immunoglobulins. A few studies only, dealing with difference in mechanisms depending on the way of administration (intravenous, oral or peribulbar) are available. Efficacy of the three ways of application is statistically different. The systemic administration of steroids has a higher efficacy than the local peribulbar application. Furthermore, evidence based and compared to the oral form, the intravenous steroid administration shows both a significantly higher response rate as well as markedly less adverse events. Thus, high dose intravenous steroid pulses are currently considered the first line-treatment for active and severe GO.