Chronic infections in the respiratory tracts of cystic fibrosis (CF) patients are important to investigate, both from medical and from fundamental ecological points of view. Cystic fibrosis respiratory tracts can be described as natural environments harbouring persisting microbial communities with Pseudomonas aeruginosa as a dominant pathogen. Various factors contribute to the complexity of this ecosystem, including community composition, dynamics and interactions, as well as heterogeneous distribution and fluctuation of components of the immune system, antibiotics and nutrients. All these elements constitute the selective forces that drive the evolution of the microbes after they migrate from the outer environment to human airways. Pseudomonas aeruginosa adapts to the new environment through genetic changes and exhibits a special lifestyle in chronic CF airways. Understanding the persistent colonization of microbial pathogens in CF patients in the context of ecology and evolution will expand our knowledge of the pathogenesis of chronic infections and improve therapeutic strategies.