Pseudomonas aeruginosa is the most important pathogen in the lungs of cystic fibrosis (CF) patients. Chronic colonization by this bacterial pathogen constitutes the major cause of morbidity and mortality in CF populations. Most importantly, P. aeruginosa infections generally persists despite the use of long-term antibiotic therapy, since antibiotic treatment rarely results in complete eradication of the infection. I am interested in understanding the mechanisms that mediate antibiotic resistance in P. aeruginosa CF and chronic infections. Specifically, I am exploring two different hypothesis: the first one links antibiotic resistance to the ability of P. aeruginosa to form biofilms in the CF lung. The second hypothesis postulates that factors within the CF respiratory tract, such as prolonged antimicrobial therapy and nutritional limitations, select for P. aeruginosa phenotypic variants with increased resistance to antibiotics.