Metabolomics aims to profile all the small molecule metabolites found within a cell, tissue, organ or organism and use this information to understand a biological manipulation such as a drug intervention or a gene knock out. While neither mass spectrometry or NMR spectroscopy, the two most commonly used analytical tools in metabolomics, can provide a complete coverage of the metabolome, compared with other functional genomic tools for profiling biological moieties the approach is cheap and high throughput. In diabetes and obesity research this has provided the opportunity to assess large human populations or investigate a range of different tissues in animal studies both rapidly and cheaply. However, the approach has a number of major challenges, particularly with the interpretation of the data obtained. For example, some key pathways are better represented by high concentration metabolites inside the cell and thus, the coverage of the metabolome may become biased towards these pathways (e.g. the TCA cycle, amino acid metabolism). There is also the challenge of statistically modeling datasets with large numbers of variables but relatively small sample sizes. This perspective discusses our own experience of some of the benefits and pitfalls with using metabolomics to understand diseases associated with type II diabetes.