Central arterial stiffening is both an indicator and an initiator of cardiovascular disease, and aging is a ubiquitous cause of stiffening. In this talk, we will discuss the utility of biomechanical models in understanding particular effects of arterial stiffening on systemic hemodynamics and we will discuss advantages of using mouse models to obtain detailed longitudinal information on regional variations in arterial wall properties. In particular, we will focus on delineating intrinsic material and structural stiffness as a function of location along the aorta and we will show results from 3-D computational simulations of the hemodynamics that account for interactions between the blood and regional wall properties. Amongst the different findings, one emerging concept is that adaptive responses appear to favor the maintenance of material stiffness near normal values while offsetting increased hemodynamic loads or genetic defects with changes in structural stiffness. If true, such a response would have important mechanobiological implications.