Dysregulated neutrophilic inflammation and chronic infection lead to progressive destruction of the airways in cystic fibrosis (CF). Despite considerable recent progress in therapy, the median survival of patients with CF remains around 30 years. The lipoxins are endogenous anti-inflammatory lipid mediators that are important regulators of neutrophilic inflammation. Recent data indicate that there is a pathophysiologically important defect in lipoxin-mediated anti-inflammatory activity in the CF airway, suggesting novel approaches to pathogenesis and therapy in this lethal genetic disease.