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Lung disease in cystic fibrosis (CF) results from chronic airway infection and inflammation leading to progressive bronchiectasis and respiratory failure. Bacterial pathogens, including Pseudomonas aeruginosa, Staphylococcus aureus, and Burkholderia cepacia, are known contributors. Recent studies using culture-independent molecular techniques and anaerobic cultures have broadened our view of CF airway bacterial communities.Sanger sequencing, high-throughput pyrosequencing, and phylogenetic microarray analysis have been used to comprehensively examine the airway microbiome in CF. Findings confirm that CF airway bacterial communities are highly complex structures with anaerobes frequently present. Importantly, there is evidence that loss of community diversity and richness is associated with older age and decreased lung function in CF. Bacterial communities are also likely influenced by antibiotic use, chronic P. aeruginosa infection, host genetic background (ΔF508 CFTR mutation) and geographic variations. Quantitative anaerobic cultures also detect high quantities of anaerobes from CF airway samples, including during pulmonary exacerbations. The effect of antimicrobial therapy on the airway microbiome needs further investigation. In addition, probiotic approaches have been recently studied; whether probiotics act by altering microbial communities or by modulating host inflammatory response is unknown.Complex bacterial communities, including traditional CF-associated pathogens and anaerobic bacteria, are common in CF airways. Novel therapeutic approaches aimed at modulating airway bacterial communities may lead to improved treatment of CF lung disease.