Glucocorticoids (GCs) are potent anti-inflammatory and immunosuppressive agents. They act by two different mechanisms: the genomic and the non-genomic pathways. The genomic pathway is considered responsible for many adverse effects of GCs, most of them are time and dose dependent. Observational studies support a relationship between GCs and damage in SLE. GCs have been associated with the development of osteoporosis, osteonecrosis, cataracts, hyperglycaemia, coronary heart disease and cognitive impairment, among others. Although no clinical trial has compared high vs low doses of GCs, some studies have shown the efficacy of medium doses in severe forms of SLE. The dose below which treatment can be considered safe has not been defined, but daily doses <7.5 mg of prednisone seem to minimize adverse effects. Combination therapy with HCQ and the judicious use of immunosuppressive drugs help to keep prednisone therapy within those limits.