C-reactive protein (CRP), a blood marker of inflammation and a hallmark of the acute-phase response, has been shown to be a powerful and specific predictor of cardiovascular event risk in populations of otherwise healthy persons. Here we review what is known about CRP gene polymorphisms, discuss how these might affect the epidemiology of CRP and our understanding of CRP's contribution to cardiovascular disease, and examine their potential clinical usefulness. Evidence shows that certain subtle variations in the CRP gene sequence, mostly single nucleotide polymorphisms, predictably and strongly influence the blood level of CRP. Some of these variations are associated with clinical correlates of cardiovascular disease. If future studies can establish with certainty that CRP influences cardiovascular biology, then CRP gene profiling could have clinical utility.