Despite the emerging evidence suggesting a proatherogenic role of C-reactive protein (CRP) in atherosclerosis, the contribution of CRP in pathogenesis of atherosclerosis and atherothrombosis has not been unequivocally defined. The role of CRP in pathophysiology/pathology seems to largely depend on its structure. Two CRP isoforms, the native pentameric and the modified monomeric one, differ substantially in their physiological functions, which is thought to origin from the considerable structural heterogeneity of the CRP molecule. The present review provides an overview of the experimental evidence with relevance to the clinical role(s) of various CRP isoforms. The biological role of the protein, its structure and distribution are discussed with particular emphasis on the diverse properties of the pentameric and monomeric forms of CRP. Some methodological aspects, related to experimental models and techniques of CRP preparation, are also critically reviewed.