Metabonomics is a powerful holistic approach for biomarker discovery and an effective tool for pinpointing endpoint metabolic effects of external stimuli, such as pathogens. Therefore, metabonomics is a promising method to enhance our understanding of infection mechanism, and holds potential for discovery of novel targets for diagnostics, drugs and vaccines. Due to advances in metabonomics technology, emerging research on infectious diseases in the past decade has been reported. In this review, we emphasise the importance of host metabolic responses to infectious pathogens, including viruses, bacteria and parasites, in the understanding mechanism of infection and potential for diagnostic capability. Researches carried on cell, animal and human models are included. Finally, we conclude with a section on research needs for improved analytical techniques and integrative systems biological approach for in-depth understanding mechanisms of infection.