Optimal management of acute exacerbations of pulmonary symptoms in patients with cystic fibrosis remains questionable. The underlying cause of such exacerbations has not been identified, and the microbiology of the sputum does not differ substantially during these exacerbations. Despite the absence of conclusive evidence that antibiotic therapy enhances treatment of cystic fibrosis, the consensus favors its use. Various combination and single-agent therapies with aminoglycosides, cephalosporins, and beta-lactam antibiotics are reviewed critically. The importance of high activity against Pseudomonas strains is addressed, as is the potential value of antibiotic prophylaxis. The drawbacks of aminoglycoside treatment are reported. No evidence proves the superiority of combination therapy over monotherapy. Recent results suggesting the effectiveness of monotherapy with piperacillin or ceftazidime are encouraging and deserve follow-up to test continued efficacy and the absence of development of resistant antibiotic strains. Further investigation into the prevention of acute pulmonary exacerbations in cystic fibrosis is essential.