Newborn screening for cystic fibrosis has been carried out for over 25 years, and clinical and cost benefits have been documented. There is still much variation in the methods and strategies adopted. All current screening programmes use a measurement of immunoreactive trypsin as a primary screening test, and in most, a second tier test involves analysing DNA mutations. The choice of DNA mutations depends on the genetic background in the region, and considerations of cost. Using DNA analysis as part of a screening procedure has introduced unwanted carrier detection, and protocols have now been devised in an attempt to avoid this. There are at least seven distinct protocols in use, all of which have different advantages and disadvantages, and no method or strategy will suit every region. Further careful study of performance and costs of various strategies is needed.