Nuclear magnetic resonance (NMR) spectroscopy can nondestructively evaluate changes in metabolites with different disease states, as well as with therapeutic interventions. Animal studies have provided the basis for understanding changes in high-energy phosphates with myocardial ischemia. Studies of graded ischemia due to partial coronary stenosis have shown the sensitivity of the ratio of phosphocreatinine to inorganic phosphate to small reductions in myocardial blood flow and its relation to myocardial function. The application of NMR spectroscopy to humans requires precise localization techniques to avoid acquiring contaminating information from structures around the heart, such as the chest wall and diaphragm. With these localization techniques, metabolic evidence of ischemia has been demonstrated in patients with myocardial infarction and patients with known coronary disease, although the sensitivity of this technique for the diagnosis of inducible ischemia is unknown. At rest, patients with dilated and hypertrophic cardiomyopathies often have an elevated phosphodiester resonance, possibly signifying abnormal breakdown of membrane phospholipids. Increasing oxygen demand in these patients does not usually alter high-energy phosphates, suggesting that oxidative energy metabolism is preserved under these conditions. NMR spectroscopy is a powerful tool to increase understanding of metabolic changes in a variety of pathologic conditions.