It is becoming increasingly clear that arterial stiffness may be determined not only by age(ing) and blood pressure, but also by exposure to other cardiovascular risk factors. This chapter reviews the evidence provided by studies adopting an aetiological model of analyses of determinants of arterial stiffness, mainly derived, if available, from prospective designs. Specifically, the following risk factors are examined: the critical axis (central) obesity – metabolic syndrome – (type 2) diabetes, and also smoking. There is convincing evidence, reinforced by recent aetiological prospective studies, that these risk factors, all of which may be preventable, increase arterial stiffness. This may explain, at least in part, the increased cardiovascular disease risk observed in these conditions. However, the molecular basis of greater arterial stiffness associated with these risk factors remains to be fully elucidated. In addition, the prognostic significance of arterial stiffness indices in individuals with these risk factors, and the extent to which intervention on these risk factors improves cardiovascular outcome through beneficial impact on arterial stiffness, is still unclear. Given the high and/or increasing prevalence of these risk factors, these issues constitute an important research agenda.