The cystic fibrosis lung is inflamed and therefore the impact of inflammation on CFTR rescue should be considered. There is now evidence that airway inflammation enhances CFTR rescue. The development of CFTR modulators, such as correctors that augment F508del CFTR transfer to the apical membrane, and potentiators that increase CFTR channel activity, permitted successful treatment of the basic defect in cystic fibrosis. The first FDA-approved CFTR modulator was the potentiator ivacaftor (VX-770), which improves the function of the gating mutant G551D CFTR. While the potentiator VX-770 or the CFTR corrector lumacaftor (VX-809) alone did not significantly improve lung function in F508del CF patients, combining VX-809 with VX-770 (in the drug Orkambi) or combining the newer corrector tezacaftor (VX-661) with VX-770 (in the drug Symdeko) resulted in modest lung function improvements in clinical trials in patients homozygous for F508del CFTR. Notably, F508del rescue resulting from these combination therapies or the clinically effective novel triple therapy (in the drug Trikafta) were enhanced by airway epithelial inflammation in vitro. Thus, the airway inflammatory milieu improves the efficacy of CFTR modulators.