This review of the genetics and molecular mechanisms of cystic fibrosis emphasizes recent progress and recounts the historical background that made these new advances possible. This review of the genetics and molecular mechanisms of cystic fibrosis emphasizes recent progress and recounts the historical background that made these new advances possible. Advances in the care of patients with cystic fibrosis have improved survival, and as a result, patients with the disease now often live beyond the third decade. 1 In addition, developments in the understanding of the genetics and molecular mechanisms of cystic fibrosis have led to new targets for treatment and an increasingly hopeful outlook. This review summarizes the mechanisms underlying the disease, the sequelae stemming from the absence of a functioning cystic fibrosis transmembrane conductance regulator (CFTR), and the therapeutic strategies devised to correct these abnormalities. Progress in the supportive care of patients with the disease has been reviewed elsewhere. . . .