Antibiotics are administered to patients with cystic fibrosis to eliminate or suppress sputum bacteria. Aerosol administration is attractive because it delivers antibiotic directly to the site of infection. Effective aerosol administration is compromised by the inefficiency of nebulizers to generate small-particle aerosols, adverse airway reaction to the drug, potential emergence of resistant bacteria, and cost. Studies evaluating aerosol treatment have not always controlled for confounding factors and have used a variety of outcome indicators. Results of controlled studies are contradictory with regard to the beneficial effect of aerosol therapy on pulmonary function, sputum bacterial density, and frequency of hospitalization. Therefore, until additional well-controlled trials are completed, routine aerosol administration of antibiotics in cystic fibrosis is not warranted because of cost, potential side effects, and the propensity to select resistant organisms.