Glucocorticoids (GCs) constitute a first line treatment for many autoimmune and inflammatory diseases. Due to their potent anti-inflammatory and immunosuppressive actions, GCs are added frequently to disease modifying antirheumatic drugs (DMARDs) in various arthritic diseases, such as rheumatoid arthritis. However, their prolonged administration or administration at high doses is associated with adverse effects that may be (quality of) life-threatening, including osteoporosis, metabolic, gastrointestinal and cardiovascular side effects. In this review, we summarize the clinical and pharmacological effects of GCs in different arthritic diseases, while documenting the current research efforts towards the identification of novel and more efficient GCs with reduced side effects.