In most developed countries 25% of adults with asthma are current cigarette smokers. Asthma and active cigarette smoking interact to cause more severe symptoms, accelerated decline in lung function, and impaired short-term therapeutic response to corticosteroids. Cigarette smoking may modify inflammation that is associated with asthma, although there are limited published data on airway pathology in smokers with asthma. To date, the evidence points towards a combination of both heightened and suppressed inflammatory responses in smokers compared with nonsmokers with asthma. The mechanisms of corticosteroid resistance in asthmatic smokers are unexplained, but could be as a result of alterations in airway inflammatory cell phenotypes, changes in the glucocorticoid receptor-a to b ratio and increased activation of pro-inflammatory transcription factors or reduced histone deacetylase activity. In conclusion, asthmatics who smoke should be strongly encouraged to stop, although the effects of smoking cessation upon reversing the adverse effects of tobacco smoke on asthma control, therapeutic response to corticosteroids and airway pathology have yet to be fully elucidated. Furthermore, alternative or additional therapies to inhaled corticosteroids are needed for asthmatic patients who are unable to quit smoking, and it seems that there may be a need for reassessment of current treatment guidelines in this population. Pneumon 2006, 19(3):202-215