The aim of this paper is to review the pathophysiological role of paraoxonases: PON-1, PON-2 and PON-3, in the development of diseases related to aging and lipid peroxidation, mainly in atherosclerosis and cardiovascular diseases, diabetes mellitus, neurodegenerative diseases (Alzheimer’s disease, Parkinson disease, multiple sclerosis) and cancer. This evidence concerns the gene PON2 and early-onset autosomal dominant Alzheimer disease.