Cystic fibrosis (CF) should be considered in patients with a wide variety of clinical presentations and of diverse racial and ethnic backgrounds. In most cases the diagnosis is suggested by manifestations of chronic sinopulmonary disease and exocrine pancreatic insufficiency, and then confirmed by a positive sweat test result. Patients may, however, present with pancreatic sufficiency or other atypical clinical features, sometimes in association with normal or borderline sweat test results. In such cases, the ability to detect CF mutations and to measure transepithelial bioelectric properties can be diagnostically useful. Mutation analysis can also be used for carrier screening, prenatal diagnosis, and newborn screening.