The goal of this review is to highlight current advances in the non-invasive detection of clinically significant atherosclerotic disease including the so-called vulnerable plaque with computed tomography. Atherosclerotic disease encompasses stages of plaque progression, stabilization, and even regression. Traditionally, the focus of diagnostic imaging has been the detection of lumen-occluding atheroma. However, advances in our understanding of the pathophysiology of atherosclerotic plaque have shown that, in certain stages of plaque progression, plaque is "vulnerable" and able to cause acute coronary syndromes despite "non-significant" vascular occlusion at baseline. This provides a rationale to improve our non-invasive imaging technology. Presented here are improvements in soft-tissue resolution with technical advancements as well as contrast-enhancement and lately even nanotechnology-based technology which are geared to detect the clinically elusive vulnerable plaque and provide an opportunity for preventative therapy.