Multiple strategies are available for clinicians to identify patients at high risk for cardiovascular events. Two commonly discussed strategies are the identification of vulnerable plaques and the identification of vulnerable patients. The strategy of identifying vulnerable patients is less invasive, easy to implement and not restricted primarily to one vascular bed (e.g. coronary or cerebral). This review discusses the utility as well as the limitations of global risk assessment tools to identify such patients. The utility of biomarkers [C-reactive protein, lipoprotein-associated phospholipase A(2) and lipoprotein(a)] and non-invasive measures of atherosclerosis burden (coronary artery calcium scores, carotid intima-media thickness and ankle-brachial index) in identifying patients at high risk for cardiovascular events are also discussed.