Cystic fibrosis (CF) pathophysiology is hallmarked by excessive inflammation and the inability to resolve lung infections, contributing to morbidity and eventually mortality. Paradoxically, despite a robust inflammatory response, CF lungs fail to clear bacteria and are susceptible to chronic infections. Impaired mucociliary transport plays a critical role in chronic infection but the immune mechanisms contributing to the adaptation of bacteria to the lung microenvironment is not clear. CFTR modulator therapy has advanced CF life expectancy opening up the need to understand changes in immunity as CF patients age. Here, we have summarized the current understanding of immune dysregulation in CF.