Aggressive antibiotic therapy of bacterial airway infection is one of the main reasons for the dramatic increase in life expectancy over the last few decades. Staphylococcus aureus and Haemophilus influenzae are the predominant pathogens in younger patients, but the choice of antibiotic therapy against these pathogens remains highly controversial. There is general agreement that patients with pulmonary exacerbations should be treated and many cystic fibrosis (CF) centres will also try to eradicate bacteria in the absence of symptoms. Prophylactic antibiotic therapy, with anti-staphylococcal medications started at the time of diagnosis, is advocated by some groups but its positive effect remains unproven. In fact, recent studies have suggested that continuous prophylactic treatment with anti-staphylococcal antibiotics may increase the risk of early colonisation with Pseudomonas aeruginosa. P. aeruginosa is the main pathogen in older children with CF. While chronic airway infection with mucoid P. aeruginosa is considered irreversible, both the combination of oral ciprofloxacin with inhaled colistin and inhaled tobramycin alone has been used successfully in the early phase of colonisation. In patients chronically infected with P. aeruginosa, standard treatment of pulmonary exacerbations consists of intravenous combination therapy for 2-3 weeks. Controversy exists whether this treatment should be performed routinely every 3 months or only in the presence of a pulmonary exacerbation. Inhaled antibiotics such as tobramycin have been shown to improve lung function and reduce sputum density of P. aeruginosa, but both the optimal dose and the duration of therapy are unclear at the present time.