The data synthesized and presented in this review were obtained by searching the databases (literature), using the following keywords: cystic fibrosis, CFTR, modifier genes, phenotypic variability in CF, candidate gene studies, genome-wide association studies (GWAS) or whole exome sequencing (WES), and CF-associated comorbidities (CF lung disease, meconium ileus (MI), CF-associated liver disease (CFLD), pancreatic insufficiency (PI), and CF-related diabetes (CFRD)) (Table 1). The gene discussed is CFTR; the disease is lung disorder.