Metabolites reflect the dynamic processes underlying cellular homeostasis. Recent advances in analytical chemistry and molecular biology have set the stage for metabolite profiling to help us understand complex molecular processes and physiology. Metabolomics is the comparative analysis of metabolite flux and how it relates to biological phenotypes. As an intermediate phenotype, metabolite signatures capture a unique aspect of cellular dynamics that is not typically interrogated, providing a distinct perspective on cellular homeostasis. To date, there have been only a few metabolomics studies investigating cardiovascular diseases. In this review, we explore the principles of metabolomics and how it can provide further insight into the mechanisms of cardiovascular physiology and ultimately lead to improved diagnostic and therapeutic options for patients with cardiovascular disease.