Significant progress has been made in treating people with CF (pwCF) due to advancements in personalized approaches to correcting the underlying genetic defect of a mutated chloride channel at the apical epithelial cell surface. After initial characterization of the cystic fibrosis transmembrane conductance regulator (CFTR) protein and how it undergoes pathological misfolding resulting in abrogation of chloride transport, precise small molecule correctors and potentiators were developed which effectively bind to the protein and overcome protein misfolding and channel function. Clinical trials followed, demonstrating efficacy in pwCF in terms of improved lung function and reduced sweat chloride. While highly effective for ~85% of the CF population, some pwCF remain ineligible for modulator therapy based on CFTR mutations which are not expected to respond to modulators. Personalized medicine for these individuals now includes approaches using patient-derived tissue to study each unique CFTR mutation genotype-phenotype correlation and patient-derived induced pluripotent stem cells (iPSCs) containing corrected CFTR. Delivery of corrected CFTR is proceeding with clinical trials using gene addition by viral vector delivery systems, mRNA lipid nanoparticles, antisense oligonucleotides, and gene editing. The overarching goal of this personalized approach is a precise CFTR correction for all pwCF, finally now appearing on the horizon.