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. In this review, we have systematically identified clinical articles relevant to cardiovascular disease in diabetes from the last 10 years. Our aim was to outline the structure, function and regulation of metalloproteinases and their key roles in cardiomyopathy and vasculopathy in diabetes. We also explore the effects of drug intervention on both human subjects with diabetes and experimental animal models. The modulation of MMP and TIMP activity using drugs that affect the expression and function of these proteins may provide us with new ways to treat this serious and disabling disease, and we explore potential mechanisms and treatments.