New serologic markers of cardiovascular risk continue to be amassed. Among the new markers, C-reactive protein, fibrinogen, and homocysteine have enjoyed the most acceptance, but newer concepts such as inflammatory cytokines, aspirin resistance, and antioxidant deficiency continue to emerge. Traditional cardiac risk factors are able to predict less than half of cardiovascular events, and the new array of markers have added little to clinical practice, with their use and significance remaining unclear. This article analyzes the new serologic markers of risk in light of the mechanistic, epidemiologic, and clinical data collected over the past decade, and in so doing provides a comprehensive understanding of their role.