The concept of the vulnerable patient has arrived. Enhanced diagnostic methods will eventually permit accurately finding and treating these patients and their disease. Clinical Cardiologists now recognize that coronary atherosclerosis is two pathophysiologically distinct syndromes: stable and unstable. Stable coronary syndromes result from fixed, severe stenoses limiting blood flow and causing secondary myocardial ischemia. The unstable acute coronary syndromes are frequently catastrophic and are pathophysiologically distinct. They result from different cell subsets causing vascular inflammatory syndromes rather than gradual lumen constriction by plaque. Though pathophysiologically distinct, they may show common pathophysiology when a ruptured plaque heals and progressively becomes a critical stenosis. For the present hs-CRP measurement is the strongest correlative factor for future clinical events due to arterial inflammation: myocardial infarction, unstable angina, stroke, and peripheral vascular disease in both diseased and apparently healthy, asymptomatic patients. The CRP plasma level also is the best risk assessment in patients with either stable or unstable angina, long term after myocardial infarction, and in patients undergoing revascularization therapies. One study showed the only independent cardiovascular risk indicators using multivariate, age adjusted and traditional risk analysis were CRP and Total/HDL cholesterol ratio. If CRP, IL-6, and ICAM-1 levels are added to lipid levels, risk assessment can be improved over lipids alone. The prevalence of high-risk subjects in the general population is low, amplifying diagnostic problems for vulnerable plaque. Since no test yet has high sensitivity or specificity, diagnostic errors are high, with many false positives and negatives. Sensitivity or specificity must be increased by developing a risk marker panel, or by simultaneously finding other markers that themselves are highly sensitive and specific for vulnerable plaque.