The metabonomic approach to biological analysis has demonstrated considerable success in obtaining and decoding metabolic signatures of health, disease and biological challenge. The rise of metabonomics to join the principal 'omics' streams in medical research has been enhanced in particular over the last 10 years by developments in modelling methods, rather than simply via advances in the supporting analytical platforms and biosampling modalities. Metabonomic analysis has been applied in a diverse range of areas from toxicology and dietary effects through to parasitology and molecular epidemiology, and promises yet further advances and wider future application. Some of the basis and methodology of this success is discussed, and some analytical sampling options, future modelling techniques and new targets, and 'blue skies' possibilities are presented in the context of personalised health and the delivery of optimised medical care to individuals. Metabonomics will continue to contribute significantly to improving our knowledge of a wide range of biological systems.