Interest in C-reactive protein (CRP) and the association of its serum level in apparently healthy individuals to their cardiovascular disease risk has soared over the past decade. Recent studies have shown that the interindividual variations in CRP levels not only reflect environmental cues but are also a consequence of the genetic variation in the CRP gene itself. The importance of the relationship of CRP gene variants to CRP serum level and cardiovascular disease risk is important to establish CRP gene profiling as a clinical risk prediction tool and also to help test the cause-effect relationship between CRP and vascular disease. This article reviews recent studies that address the relationship of CRP gene polymorphisms to inflammation and cardiovascular risk.