Knowledge of the microbiology of pulmonary infections is critical for treatment of cystic fibrosis because sickness and mortality in this disease are mainly due to relapse occurring in the respiratory tract. The microbiology of pulmonary infections presents several singular aspects. Respiratory tract infections are caused by bacteria such as Staphylococcus aureus in the early years of life and Pseudomonas aeruginosa and Burkholderia cepacia thereafter. The patients, who are not immune compromised, are predisposed to chronic colonization and highly transmissible bacterial strains can cause cross-infections. Bacterial also develop resistance mechanisms which make them difficult to treat. Until recently the relationship between genetic defects and a predisposition to colonization was not noted, but recent studies have allowed us to form some interesting hypothesis. The present work analyzes the principal mechanisms of antibiotic resistance, with particular reference to classic cystic fibrosis pathogens, and looks at future prospects of respiratory tract infection treatment.