Despite the exciting breakthroughs in the development of CFTR modulator therapy, this therapy is not effective for all patients with cystic fibrosis. Only patients with at least one F508del allele can benefit. In this digest we have discussed how innovators are now moving beyond conventional EnAC to small-molecule CFTR modulator drug therapy, RNAi, stem cells, gene delivery vectors, and CRISPR/Cas9 gene editing for future therapies.