Treatment for acute asthma exacerbations is a major need not adequately met by current therapies. Although virus infections are the major cause of acute exacerbations, other factors can increase the risk/severity of exacerbations. Increasing evidence suggests atypical bacterial infections contribute to exacerbation severity, as well as stable asthma, particularly severe asthma. Macrolide antibiotics and the new ketolide antibiotic telithromycin are active against atypical bacteria and also have anti-inflammatory activity. A recent study has shown telithromycin to be effective in the treatment of acute exacerbations of asthma, although the mechanism or mechanisms of action were not determined. Controlled studies report small improvements in lung function with macrolide treatment of stable asthma. Further studies are urgently required to assess the role of such therapies in acute exacerbations and in severe stable asthma, in which the risk/benefit ratios are likely to be most in favor of therapy demonstrated to be effective.