Cystic fibrosis (CF), the most common autosomal recessive disorder in Caucasians, and chronic obstructive pulmonary disease (COPD), a disease of adults, are characterized by chronic lung inflammation, airflow obstruction and extensive tissue remodelling, which have a major impact on patients' morbidity and mortality. Airway inflammation is stimulated in CF by chronic bacterial infections and in COPD by environmental stimuli, particularly from smoking. Pseudomonas aeruginosa is the major bacterial pathogen in CF, while in COPD, Haemophilus influenzae is most frequently observed. Molecular studies indicate that during chronic pulmonary infection, P. aeruginosa clones genotypically and phenotypically adapt to the CF niche, resulting in a highly diverse bacterial community that is difficult to eradicate therapeutically. Pseudomonas aeruginosa clones from COPD patients remain within the airways only for limited time periods, do not adapt and are easily eradicated. However, in a subgroup of severely ill COPD patients, P. aeruginosa clones similar to those in CF persist. In this review, we will discuss the pathophysiology of lung disease in CF and COPD, the complex genotypic and phenotypic adaptation processes of the opportunistic bacterial pathogens and novel treatment options.