Cardiovascular diseases are the main causes of death and disability worldwide and are caused mainly by the chronic accumulation of atherosclerotic plaque in the arteries. Intense investigation over 4-5 decades has advanced our understanding of what causes the formation of atherosclerotic plaques and their progression, rupture, healing and hardening due to fibrosis and calcification. Plaque therapies have also been developed. It is thus essential for both diagnostic and treatment to be able to quantify through imaging the progression of plaque size and composition in critical areas such as the carotids, coronary arteries and inferior limbs. The focus of the presentation will be quantifying the atherosclerotic plaque and determining its composition in association with different human disease processes, with the two main medical imaging modalities, MRI and CT. We will also present how the effect of therapies designed to alter plaque size and composition can be monitored by imaging techniques and what are the physical requisites in terms of spatial and temporal resolution, tissue coverage, the need for gating to control for cardiac and/or respiratory motion, and other aspects required for detection and monitoring of atherosclerotic plaques clinically. The presentation will discuss also the possibility to use phase-contrast X-ray imaging (PXI) to image atherosclerosis, monitor its alterations in response to natural historical processes and treatment, with an eye to eventually treat it through energy deployment with laser guided accuracy.