Free fatty acids (FFAs) serve as physiologically important energy substrates and their release from the adipose tissue by lipolysis is regulated according to the energy demands of the body. FFAs are increased in obese patients and contribute to type 2 diabetes, hepatic steatosis and several cardiovascular diseases. In patients with heart failure and acute coronary syndromes, elevated FFA levels are a consequence of an increased lipolysis due to a surge in catecholamines and natriuretic peptides. FFAs contribute to myocardial dysfunction and are proarrhythmic, and their oxidation requires more oxygen than does glycolysis. Therapeutic approaches have already emerged that aim to reduce the uptake and/or oxidation of fatty acids in the myocardium. The routine use of FFAs as a diagnostic tool is limited by their high variability, this being strongly influenced by nutrition and the effects of several hormones. In addition, it remains to be clarified whether fasting or postprandial values or dynamic measurements such as changes in FFA concentrations induced by stress are better parameters for evaluating cardiovascular risk. In this review, we present an overview of the metabolism and role of FFAs as a cardiovascular risk factor and discuss the potential of FFAs in the diagnosis and treatment of cardiovascular diseases.