The introduction of tandem mass spectrometry has unquestionably been the most striking recent advance in newborn screening. A single test is applied for the simultaneous diagnosis of a number of disorders, making it possible to screen for some disorders that might otherwise have seemed too rare. Current screening is for disorders of metabolism of amino acids, organic acids and fatty acids. Assay performance for detection of disorders appears very good, but rarity of disorders, varied definitions and systems for follow-up and lack of databases for inborn errors of metabolism diagnosed clinically means that there is as yet insufficient information about most disorders. The technology can be applied to a much wider range of compounds, and the field looks set to expand. A key feature of newborn screening programmes must be the assessment of outcomes, and a major reason for the lack of uniformity in the approach adopted in different countries is the paucity of information on this. The available evidence points to overall advantages flowing from early diagnosis by screening, with reduction in mortality and morbidity. More studies are clearly needed and some are under way. The next new group of disorders already proposed for newborn screening is the lysosomal storage disorders. Attitudes may be changing about what it is desirable to include in a newborn screening programme, and this will indeed pose new ethical dilemmas.