Glucocorticoids (GC) are effective drugs which are often used in rheumatology. However, they have a considerable potential for frequent and sometimes serious side effects that restrict their use. Their mechanisms of action are either receptor dependent (specific) or independent (unspecific) on the genomic as well as the non-genomic level. Many adverse effects are predominantly caused by transactivation while the desired effects are mostly mediated by transrepression. Treatment strategies are sub-classified into low, medium, high, very high dose and pulse therapy based on criteria such as dose, indication, duration of treatment and potential risk of adverse events. The musculoskeletal, gastrointestinal, neuro-endocrino-immunological, opthalmological and neuropsychiatric systems are examples where adverse effects may occur.