CFTR modulators have been a groundbreaking new invention starting with the approval of the CFTR corrector Ivacaftor in 2012. Nowadays, up to 90% of CF patients have the potential ability to get treated by an appropriate CFTR modulator. Ivacaftor showed significant improvement in the treatment of CF patients with gating mutations, especially in G551D mutations. The combination of Elexacaftor, Tezacaftor and Ivacaftor showed tremendous benefits because it is appropriate for a broad spectrum of variant mutations, importantly to mention being effective in F508del mutations no matter if homozygous, heterozygous or with a minimal function mutation. An early administration of CFTR modulators reduces the severity and extent of the clinical picture, which underlines the necessity and importance of the neonatal CF screening. A lot has been achieved up to now, and a lot is yet to come. The range of accessible CFTR modulators will be increased in the near future, since new medications are in development and already in the last phases of clinical trials. The goal is to make therapy accessible and available for all cystic fibrosis patients to achieve equality and to reduce mortality and morbidity of this lethal genetic disease.