The search for markers to improve risk prediction for individuals at risk of developing serious cardiovascular events is ongoing. New markers of coronary artery disease progression have been identified in recent years, among which, circulating levels of pregnancy-associated plasma protein-A (PAPP-A) offer an interesting profile. PAPP-A may play a role in the development of atherosclerotic lesions and represent also a marker of atheromatous plaque instability and extent of cardiovascular disease. PAPP-A has been shown to be a marker of adverse outcome in both acute coronary syndrome and stable coronary disease patients. The present article reviews currently available evidence supporting a role for PAPP-A as a marker of cardiovascular risk and discusses some of the pitfalls that may limit its use in clinical practice.