In clinical studies of CFTR modulators, including CF patients infected/colonized with P. aeruginosa, we speculate that the negative effect of P. aeruginosa on CFTR rescue contribute to the lesser clinical benefits of CFTR modulators on lung function (Wainwright et al., 2015), compared to their expected in vitro activity established in pathogen free conditions. This evidence concerns the gene CFTR and cystic fibrosis.