Paraoxonases (PON) are three enzymes (PON1, PON2 and PON3) that play a role in the organism's antioxidant system; alterations in which are associated with diseases involving oxidative stress. In this review, we summarize the evidence of PON related to the pathogenesis of coronary artery disease (CAD) and atherosclerosis. We searched three electronic databases (PubMed, Scopus and Cochrane Database) with no date limit. All of the articles selected investigated PON enzymatic activity and/or PON gene polymorphisms. The selection focused on PON in relation to atherosclerosis, CAD and myocardial infarction. The exclusion criteria were a sample size <100 patients, non-human studies, editorials and systematic reviews without restrictions on the country of origin. With these criteria, we identified thirty-five prospective studies published between 1986 and 2014 with a total of 28,164 participants. The relationship between PON gene polymorphisms and CAD was not conclusive, but most studies support the concept that alterations in PON1 enzymatic activity levels do influence atheroma formation. Conversely, relationships between PON2 and PON3 vs. CAD have not been extensively investigated. Our review of the current data concludes that the bases of paraoxonases involvement in atherosclerosis are poorly understood and that this issue requires future comprehensive, multi-centered studies.