Coronary heart disease is one of the major causes of death in developed countries. The hypothesis that peroxidation of low density lipoproteins (LDL) may be the initial step of the atherosclerotic process has promoted numerous studies aimed at investigating the mechanisms by which the body protects itself from such oxidative phenomena. Among these mechanisms we find the paraoxanase (PON) enzyme, which is quite thriving the last decades. This enzyme is principally associated with high density lipoproteins (HDL) but it also seems to help LDL to recover their antioxidant status. This paper reviews different aspects concerning the mechanisms implicated in the induction and activity of this enzyme, as well as its production, attachment to HDL, and modifications of its activity due to external factors. The use of genetic techniques, the study of the polimorphisms of the PON enzyme and the possibility of increasing paraoxonase activity by means of pharmacotherapy and/or dietary therapy open new perspectives with regard to coronary heart disease treatment and prevention.