AbstractFungi are increasingly recognised to have a significant role in the progression of lung disease in Cystic fibrosis with Aspergillus fumigatus the most common fungus isolated during respiratory sampling. The emergence of novel CFTR modulators has, however, significantly changed the outlook of disease progression in CF. In this review we discuss what impact novel CFTR modulators will have on fungal lung disease and its management in CF. We discuss how CFTR modulators affect antifungal innate immunity and consider the impact of Ivacaftor on fungal disease in individuals with gating mutations. We further review the increasing complication of drug–drug interactions with concurrent use of azole antifungal medication and highlight key unknowns that require addressing to fully understand the impact of CFTR modulators on fungal disease.