Acute coronary syndromes, which are a leading cause of death worldwide, are caused by the rupture of vulnerable plaque (VP). A vulnerable patient is defined as one with a high atherosclerotic burden, a high burden of VP, a vulnerable myocardium and with a thrombogenic blood. Rupture-prone vulnerable plaques have a high inflammatory cell content and a large necrotic core (NC) covered by a thin fibrous cap (thin-cap fibroatheroma; TCFA). Mechanical weakening of the fibrous cap generally precedes plaque rupture. The PROSPECT study has shown that features associated with plaque vulnerability include large plaque burden (>70%), small luminal area (<4 mm2), and presence of TCFA. The predictive value of TCFA for subsequent CV events was low. Other features of vulnerability which require further validation include MMP activity and oxidative stress. Several genetic risk variants associated with CAD have been identified but their predictive value remains unclear. Treatment strategies for stabilizing vulnerable plaques include reducing the size of the lipid pool, stabilizing the thin fibrous cap or modulating the inflammatory process.