Atherosclerosis is an important contributor to increased cardiovascular burden in populations with and without renal disease. Paraoxonases (PON) are a group of enzymes that hydrolyse organophosphates. Recent evidence indicates a protective role for PON in patients with coronary artery disease and atherosclerosis. Although data are limited, the low enzyme activity found in patients with chronic kidney disease and renal transplants has been linked to atherosclerosis and arterial stiffness. In this paper, we review the emerging role of PON1 in the pathophysiology of atherosclerosis and arterial stiffness in patients with chronic kidney disease.