Metabolomics is the global unbiased analysis of all the small-molecule metabolites within a biological system, under a given set of conditions. These methods offer the potential for a holistic approach to clinical medicine, as well as improving disease diagnosis and understanding of pathological mechanisms. Respiratory diseases including asthma and chronic obstructive pulmonary disorder are increasing globally, with the latter predicted to become the third leading cause of global mortality by 2020. The root causes for disease onset remain poorly understood and no cures are available. This review presents an overview of metabolomics followed by in-depth discussion of its application to the study of respiratory diseases, including the design of metabolomics experiments, choice of clinical material collected and potentially confounding experimental factors. Particular challenges in the field are presented and placed within the context of the future of the applications of metabolomics approaches to the study of respiratory diseases.