Unlike numerous viruses such as the herpesviruses that infect humans early in life and may persist lifelong in latent form, long-term infections of a human host with bacteria are currently confined to a few species, namely Mycobacterium tuberculosis, Helicobacter pylori, and Pseudomonas aeruginosa. H. pylori and M. tuberculosis were already prevalent in humans in prehistoric times, but the chronic airway infections with P. aeruginosa in patients with cystic fibrosis (CF) emerged just 60 years ago. Hereunder, we review our current knowledge of the microevolution of P. aeruginosa in the CF airways, including key features of P. aeruginosa, the CF host, and their interaction within the airways. The focus will be laid upon own work executed within the frame of the Collaborative Research Centre 900 supported by the German Research Foundation (DFG), but moreover, we will summarize general knowledge and important contributions of our peers with emphasis on publications for the period 2018– 2022.