In most patients with cystic fibrosis (CF) life expectancy is limited due to a progressive loss of functional lung tissue. Already very early in life a persistent neutrophylic inflammation can be demonstrated in the airways. The cause of this inflammation, the role of CFTR and different CF specific bacteria like Pseudomonas aeruginosa are not well understood. This short review summarises the current understanding and hypothesis of the origin of this complicated process of inflammation and infection. Better understanding of this process may lead to the development of new treatment modalities of CF lung disease and consequent improvement of life expectancy.