Emerging evidence suggests an association between some asthma and pulmonary infection by the atypical organisms Chlamydia pneumoniae and Mycoplasma pneumoniae, but a causal role for infection remains unproven and controversial. Most acute exacerbations of asthma are triggered by acute infections that are due to viral respiratory pathogens, not to bacteria or atypical organisms. Administration of antibiotics for acute exacerbations of asthma has been shown to be ineffective. Most evidence linking atypical infections to asthma is consistent with a promoting role for chronic infection in producing persistent asthma symptoms. Preliminary studies suggest that prolonged (>/=6 weeks) administration of doxycycline or macrolides may eradicate C. pneumoniae from respiratory secretions and improve long term, not acute, asthma symptoms. Randomised, controlled trials are currently under way to investigate the effectiveness of these prolonged courses of macrolides and azalides (roxithromycin, clarithromycin and azithromycin) in adults with stable persistent asthma. Traditional courses (7 to 10 days) of any antibiotic are incapable of eradicating chronic C. pneumoniae or M. pneumoniae infection; furthermore, beta-lactam and sulphonamide-based antibiotics that are commonly prescribed in acute respiratory syndromes are ineffective against these atypical organisms. Unless the goal is to treat documented sinusitis associated with asthma, it is inappropriate to prescribe traditional courses of any antibiotic for acute asthma exacerbations; whether longer courses of antibiotics should be prescribed to eradicate chronic atypical infections and decrease persistent asthma severity remains to be established.