Metabolomics is the systematic and theoretically comprehensive study of the small molecules that comprise a biological sample, e.g., sera or plasma. Metabolomics, in conjunction with other "-omics" approaches, offers a new window onto the study of aging and caloric restriction. Here, we present the methodology that we are using, high-performance liquid chromatography separations coupled with coulometric electrode array detection, to probe the metabolome of aging and caloric-restricted animals. This system has unique advantages, notably sensitivity and high quantitative precision, but also has unique disadvantages, such as the ability to obtain little structural information on the metabolites of interest and limited scale-up capacity. The system also only detects redox-active compounds, which can be either a benefit or a detriment, depending on the experimental goals and design.