In this episode, Prof Chris Vorster (Director, Centre for Human Metabolomics, North-West University, South Africa), Sarah Viall (Assistant Professor, Molecular and Medical Genetics, Oregon Health & Science University, USA) and PD Dr. med. Ulrike Mütze (Consultant, Heidelberg University Hospital, Germany) join Silvia Radenkovic and Rodrigo Starosta to explore the evolving landscape of newborn screening. They discuss national and international variations in practice, how to maintain consistency and quality, and the future scope of testing – including opportunities to improve access in resource-limited settings. Authors’ opinions are their own and do not represent their institutions. Referenced papers include: Newborn screening in South Africa: the past, present, and plans for the future. Malherbe et al (2024) Clinical validation of cutoff target ranges in newborn screening of metabolic disorders by tandem mass spectrometry: a worldwide collaborative project. McHugh et al (2024) Five years of newborn screening for Pompe, Mucopolysaccharidosis type I, Gaucher, and Fabry diseases in Oregon. Viall & Held (2025) Long-term outcomes of adolescents and young adults identified by metabolic newborn screening. Mütze et al (2025) Treatment Outcomes for Maple Syrup Urine Disease Detected by Newborn Screening. Mengler et al (2024) Vitamin B12 Deficiency Newborn Screening. Mütze et al (2024) The role of exome sequencing in newborn screening for inborn errors of metabolism. Adhikari et al (2020)