Prospective observational studies have shown that arterial stiffness is a strong and independent predictor of cardiovascular disease in hemodialysis patients. Recent evidence further supports that arterial hardening predicts cardiovascular and all-cause mortality in peritoneal dialysis patients, renal transplant recipients and patients with chronic kidney disease (CKD) not on dialysis. Of note, dissociation of arterial stiffness and blood pressure reduction was related to worsened cardiovascular outcome in kidney disease patients, suggesting that arterial stiffness may not only be a predictor, but a true risk factor, representing a specific and potentially reversible pattern of outward arterial remodeling in these individuals. On this basis, arterial stiffness has emerged as a novel therapeutic target for cardiovascular risk reduction in patients with CKD; specific interventions, such as renin-angiotensin-system blockade, use of statins, and decrease of calcium-phosphate product may delay the progression of arteriosclerotic process. This article summarizes the accumulated evidence from clinical and epidemiological studies regarding the prognostic significance of arterial stiffening on cardiovascular outcomes and provides insights on possible treatment strategies for arterial stiffness attenuation in patients with CKD.