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Cigarette smoking and asthma are associated with poor symptom control and impaired therapeutic responses to corticosteroids. We summarize the clinical evidence for corticosteroid resistance, the mechanisms which could be responsible and potential management of this resistance. We also consider the effect smoking has on other drugs commonly used to treat patients with asthma.In most developed countries the prevalence of active smoking in adults with asthma is about 25%. Compared with nonsmokers with asthma, active smokers have more severe asthma symptoms, accelerated decline in lung function and impaired short-term therapeutic responses to corticosteroids. The mechanism of corticosteroid resistance in smokers with asthma is currently unexplained but could be due to alterations in airway inflammatory cell phenotypes, changes in glucocorticoid receptor α to β ratio, and reduced histone deacetylase activity. Cigarette smoking also increases the clearance of drugs such as theophylline by induction of metabolizing enzymes. Alternative or additional treatment to inhaled corticosteroids may be required for individuals with asthma who are unable to stop smoking or who have persistent symptoms following smoking cessation.Smokers with chronic asthma have a reduced response to short-term corticosteroid therapy. Every effort should be made to encourage individuals with asthma who smoke to stop. Alternative or additional therapies to inhaled corticosteroids are needed for individuals with asthma who are unable to quit smoking.