The aim of the present manuscript is to review, for each approved modulator: (1) the results of the main phase 3 randomized controlled trials that evaluated the safety and efficacy of CFTR modulators in adolescents (12–17 years) and adults (18 years and older) with CF (summarized in Table 2); (2) the findings of real-world studies conducted in France through the French CF reference center network in adults and adolescents with CF (summarized in Table 3). This evidence concerns the gene CFTR and cystic fibrosis.