Metabolomics represents a paradigm shift in metabolic research, away from approaches that focus on a limited number of enzymatic reactions or single pathways, to approaches that attempt to capture the complexity of metabolic networks. Additionally, the high-throughput nature of metabolomics makes it ideal to perform biomarker screens for diseases or follow drug efficacy. In this Review, we explore the role of metabolomics in gaining mechanistic insight into cardiac disease processes, and in the search for novel biomarkers. High-resolution NMR spectroscopy and mass spectrometry are both highly discriminatory for a range of pathological processes affecting the heart, including cardiac ischemia, myocardial infarction, and heart failure. We also discuss the position of metabolomics in the range of functional-genomic approaches, being complementary to proteomic and transcriptomic studies, and having subdivisions such as lipidomics (the study of intact lipid species). In addition to techniques that monitor changes in the total sizes of pools of metabolites in the heart and biofluids, the role of stable-isotope methods for monitoring fluxes through pathways is examined. The use of these novel functional-genomic tools to study metabolism provides a unique insight into cardiac disease progression.