We review the current situation with respect to newborn cystic fibrosis screening (NCFS) across the world. The challenges of establishing an NCFS programme are reflected in the diversity of those programmes identified. All employ an initial immunoreactive trypsinogen (IRT) measurement during the first week of life. If this is positive, a second IRT analysis at 4 weeks of age improves the specificity of the test; most programmes have, however, moved to DNA analysis at this point, which improves their sensitivity. Incorporating DNA analysis results in the identification of carriers, which may have implications for families but is generally considered positive. Some programmes have incorporated a second IRT test as well as DNA analysis, either to increase the sensitivity of the test in an area with a low DeltaF508 frequency or to reduce the number of infants requiring a sweat test. Whichever algorithm is selected, the implementation of a successful programme relies on clear pathways and good information for parents.