Mutations in the human genome may result in altered phenotypes. The cystic fibrosis (CF) patient, for instance, suffers from an aberrant composition of the epithelial lining of the gastrointestinal and respiratory tract. In this particular case, a single point mutation in the cystic fibrosis conductance regulator (CFTR) gene results in major physiological changes resulting in ecological changes that generate a niche particularly attractive to a selected set of microbial pathogens. We here present a review on the dynamics of the bacterial populations inhabiting the CF lung. Studies focusing on Staphylococcus aureus, Haemophilus influenzae and Pseudomonas aeruginosa will be summarised and discussed, whereas the technology used for microbial characterisation will be shortly highlighted. Emphasis, however, will be on those studies that assessed the genetic diversity among clinical isolates that were obtained over prolonged periods of time, enabling the distinction between persistent colonisation versus frequent re-infection by the selected pathogens. Evolutionary adaptation of pathogens to the CF lung is a common theme in many of these studies.