Cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) molecule; these mutations result in a defect in chloride secretion in epithelial cell layers. The disease is characterized by severe gastrointestinal and pulmonary symptoms, but it is the pulmonary symptoms that dominate the clinical course of the disease and determine patients' life expectancy. These pulmonary symptoms include reduced mucociliary clearance, chronic inflammation, and recurrent and chronic pulmonary infections with Pseudomonas aeruginosa, Staphylococcus aureus, Burkholderia cepacia, and Haemophilus influenzae. Recent studies have shown that sphingolipids, especially ceramide, play a crucial role in the pathogenesis of cystic fibrosis. These studies have demonstrated that ceramide accumulates in the lungs of cystic fibrosis patients and mice, causing inflammation and high susceptibility to bacterial infections. The results of initial clinical studies suggest that interfering with sphingolipids may be a novel treatment strategy for cystic fibrosis.