Glucocorticoids (GCs) are a highly effective class of medication used in the treatment of airway inflammation associated with chronic asthma. Nevertheless, there remain concerns regarding potential adverse effects accompanying the use of systemic and high-dose inhaled GC therapy. Recent studies also suggest that there is high variability in airway response to GCs. Indeed, the immunopathogenesis of a subset of asthmatics poorly responsive to glucocorticoid therapy have been studied and may provide new insights into mechanisms by which glucocorticoids act in chronic asthma. The current review will examine a number of these issues, particularly mechanisms by which GCs act in asthma, the immunology of steroid resistance, and adverse effects associated with GC treatment.