Metabolomics examines the interconnected landscape of small molecules within a biological system – the metabolome – providing a time-specific snapshot of its functional state under specific conditions. While other ‘omic’ technologies primarily give us insight into ‘what is there’ (e.g., genomics and metagenomics, which tell us about genetic composition), analysis of the metabolome can help understand the functionality of a biological system in health and disease and identify signatures of pathology that may emerge earlier than traditional clinical and biochemical signs. Biological systems do not function in isolation, and metabolomics can help us understand how their activity is shaped by interactions with surrounding systems, including contributions from associated communities such as the microbiome. Continuous developments in analytical techniques have enabled the application of metabolomics to grow rapidly, including in the range of biological samples that can be examined, the metabolites that can be identified, and the reliability of collected data. Due to these advances, metabolomics has found success in numerous applications, including disease screening, diagnostics, phenotyping, and identifying new targets for intervention. We focus on exploring the very latest developments in this regard across a range of disease areas. Moving into the future, metabolomics is anticipated to play an increasingly transformative role in disease management, with emerging developments in epidemiology, large-scale screening, and – most recently – therapeutic strategies, including the identification of host and microbial metabolites that mediate and predict treatment response.