The reviewed data have been arranged into three sections involving (1) the functional relevance of PON variations (2) the impact of PON variations on lipid profile (3) the clinical relevance of PON variations consisting of five subsections: (i) coronary heart disease, (ii) stroke, (iii) diabetes mellitus, (iv) peripheral artery disease, dementia and renal disease (congregated in one subsection because of the scarce number of appropriate publications) and (v) drug response (divided into two parts: (a) antiplatelet drugs and (b) statins). Here, PON1 is linked to diabetes mellitus.