Large artery stiffening is a biological index of vascular aging. Vascular aging and atherosclerosis are two closely linked processes that develop in parallel and in synergy, sharing common aetiological determinants. Vascular stiffening increases left ventricular work and can lead to diminished coronary perfusion, and may therefore contribute to the development of cardiovascular disease. There is emerging evidence that large artery stiffness and vascular aging are accelerated in HIV infection because of the high prevalence of cardiovascular risk factors among HIV-infected patients. Moreover, the biological effects of HIV and the metabolic perturbations associated with antiretroviral therapies appear to accelerate vascular stiffening in HIV-infected patients. Further studies evaluating the effects of general and targeted therapies and various combinations of antiretroviral therapies on measures of large artery stiffness are urgently needed.