The human ascending aorta (AA) is exposed to very high shear and pressure stresses exerted by the blood flow ejected from the left ventricle outflow tract. This vessel has a unique structural behaviour which adequately redistributes the energy captured from the blood flow ejection to sustain a more continuous blood flow through the entire vascular system. Unfortunately, this vessel is prone to a pathological dilation process involving significant structural changes that can lead to fundamental modification of its mechanical behaviour and functions. Genetic and/or environmental factors have been implicated in the disease process. It is believed that in particular the forces created by blood flow (hemodynamics) can be a stimulus for vessel remodelling. For patients suffering from this deadly condition, surgical replacement or repair is the best solution to increase life expectancy. However, the replacement materials available as a treatment have a significant impact on the blood flow, the biomechanics of the aortic arch, and the entire vascular system. In this review we summarise the current understanding of the pathogenesis mechanisms involved in the dilation of the AA from a mechanical and biochemical point of view. We will also underline the needs for better replacement materials in surgical repair to improve graft patency.