Following the 2014-2016 Ebola outbreak in West Africa, and the on-going global COVID-19 pandemic, the One Health approach (bridging the Animal-Environmental-Human Health interface) has rapidly gained political and financial support, particularly in regional and transcontinental initiatives to improve Global Health Security, including through recently established institutions like Africa CDC and other multidisciplinary consortia. This four-paper Lancet Series explores the adoption of One Health approaches to improve health security and include an analysis of the current landscape of preventive, surveillance, and response measures in outbreak situations of emerging and re-emerging zoonotic infectious diseases with epidemic potential as well as other potential public health emergencies such as neglected endemic diseases, antimicrobial resistance, environmental and chemical hazards and natural disasters.