Glucocorticosteroids (GCS) are widely used to treat various inflammatory and immune diseases. The most common use of GCS today is in the treatment of asthma and other allergic diseases, and inhaled GCS have now become established as first-line treatment in adults and children who have persistent asthma. There have been major advances in understanding the molecular mechanisms whereby corticosteroids suppress inflammation, based on recent developments in understanding the fundamental mechanisms of gene transcription. This has important clinical implications, as it will lead to a better understanding of the inflammatory mechanisms of many diseases and may signal the development of new anti-inflammatory treatments in the future. The new understanding of these molecular mechanisms also helps to explain how corticosteroids are able to switch off multiple inflammatory pathways, and it also provides insights into why corticosteroids fail to work in patients who have steroid-resistant asthma and in patients who have chronic obstructive pulmonary disease.