Despite recent advances in the diagnosis of myocardial ischemia, its biochemical identification in patients with acute chest pain is still a challenge, and alternative approaches for further improvement are needed. Metabolic alterations are the first consequences of acute myocardial ischemia. Metabolomics coupled with potent multivariate analyses allows for a simultaneous and relative quantification of thousands of different metabolites within a given sample. Thus, this discipline might exert a great impact on medical practice in cardiovascular medicine by providing a wealth of relevant biochemical data. Metabolomics is a promising tool to improve current, single biomarker-based approaches by identifying metabolic biosignatures that embody global biochemical changes in disease. This is especially relevant for conditions requiring early treatment like myocardial ischemia. This review discusses the potential application of metabolomics in the diagnosis of myocardial ischemia.