Abstract Background Cystic Fibrosis (CF) is a severe genetic disorder that is common among the Caucasian population. Bacterial respiratory infections are the main cause of morbidity and mortality in CF patients. Pseudomonas aeruginosa is the main pathogen of lower airways (LAW) decline. Method To understand chronic broncho-pulmonary colonization, a systematic review is conducted. The aim of our article is to identify the pathways of contamination in the upper aero-digestive tract. Results A large number of articles report that P. aeruginosa is established first at nasopharyngeal sites. The vast majority of authors agree that the upper aero-digestive tract is the first location of colonization by P. aeruginosa and its presence appears to be predictive of subsequent broncho-pulmonary colonization. Conclusion This review supports the possible involvement of the nasal and paranasal sinuses and oral cavity as means of contamination.