Matrix metalloproteinases (MMP) and their inhibitors (TIMP) are central factors in the control of extracellular matrix turnover. They are important in normal physiology and also during a range of pathological states. Only recently has their role in cardiovascular disease been explored and their analysis through measurements in blood been studied. We have systematically identified clinical articles relevant to coronary artery disease from the last 10 years using MEDLINE. In this review we outline the structure, function and regulation of metalloproteinases and their key roles in angiogenesis, stable and unstable coronary artery disease. Metalloproteinases and their inhibitors are fundamental mediators of change in aging and atherosclerosis, the cell membrane, and in myocardial and vascular tissue. Defining their overall importance and understanding their complex interrelationships with pressure, thrombosis and local neural and hormonal tone will require detailed clinical study. The modulation of MMP and TIMP activity using drugs that affect the expression and function of these proteins will provide us with new ways to treat these serious and disabling diseases, and we explore potential mechanisms and treatments.