Recent advances in our understanding of the pathophysiological mechanisms of atherosclerosis have created the need for better non-invasive imaging of vascular phenotype. Ultrasound is widely available, inexpensive, and well suited for high-throughput screening in populations that are at risk for atherosclerosis. Novel ultrasonic approaches for the diagnosis of vascular changes in atherosclerosis include (1) assessment of plaque composition by evaluation of the backscattering properties of tissue, (2) assessment of the changes in arterial wall biomechanics, (3) assessment of plaque neovascularization, and (4) molecular imaging of vascular phenotype changes on a subcellular level. It is thought that such new imaging methodologies will lead to earlier detection of atherosclerosis, and better assessment of the risk for aggressive disease progression. Novel therapies for atherosclerosis will undoubtedly become available within the next decades, and non-invasive imaging techniques will be needed for cost-efficient application of existing and new drugs.