C-reactive protein (CRP) levels are a complex phenotype with both genetic and environmental determinants. Recent work has highlighted the impact of genetic variants within the CRP gene as well as other candidate genes, often chosen for their role in the inflammatory pathway, on CRP levels. Emerging work shows the association of such genetic variants in CRP not only to CRP levels, but also to variation of CRP levels in the acute phase response. Work on the relation of genetic variants within CRP to cardiovascular disease has had varied results. Whole-genome association studies to investigate the genetic determinants of CRP levels in an unbiased manner are ongoing.