Chronic pulmonary infections contribute significantly to the morbidity and mortality of patients with CF. The primary pathogens are Pseudomonas aeruginosa (PA) and Staphylococcus aureus. Hemophilus influenzae has been isolated from a significant number of patients also. A number of the beta-lactam and aminoglycoside antibiotics reportedly have altered pharmacokinetic variables in CF. Therapy of acute pulmonary deterioration consists of intravenous antibiotics for two weeks. Antibiotic selection is based on culture and sensitivity results. Currently, the combination of a broad-spectrum penicillin and an aminoglycoside seems to provide the best results. Prophylactic antibiotics are effective if the primary isolates are sensitive to the agents used. Chronic PA infections are problematic because effective oral agents are not available. Aerosolized antibiotics do not improve results over adequate systemic therapy for acute exacerbations. Questions regarding optimal dosages, frequency, and duration of therapy remain.