Developments in both magnetic resonance imaging (MRI) technology, computer software and a huge array of potential cellular and molecular targets are a step toward the identification of high-risk carotid disease. This chapter covers the recent advances with particular respect to MRI. The carotid artery plaque is ideally suited for imaging by multicontrast MRI. The chapter discusses a variety of molecular targets that may provide improved imaging of carotid atherosclerotic plaque using MRI. The presence of neovessels is strongly associated with plaque inflammation and likelihood of rupture, presumably by allowing an alternative route for entry of monocytes and lymphocytes into the plaque. Histological studies have demonstrated that superficial thrombus superimposed on a ruptured atherosclerotic plaque characterizes those plaques at high risk of ischemic events. The chapter describes the role of matrix metalloproteinases (MMPs) in plaque instability and matrix remodeling in atherosclerotic plaques.