Macrolide antibiotic treatment can improve asthma in a subgroup of patients that remains to be clearly defined. Macrolide benefits were first suggested in two observational trials and two randomized controlled trials of azithromycin treatment for asthma. One of these RCTs and another macrolide trial suggest that the treatment effect may be greatest in patients with severe, refractory asthma. These clinical results correlate with epidemiological evidence that "C. pneumoniae" is positively associated with asthma severity and laboratory evidence that "C. pneumoniae" infection creates steroid-resistance. A recent meta analysis of 12 RCTs of macrolides for the long term management of asthma found significant effects on asthma symptoms, quality of life, bronchial hyper reactivity and peak flow but not FEV1. Evidence from macrolide RCTs of patients with uncontrolled severe and refractory asthma will be critical in defining the role of macrolides in asthma.