Advances in the understanding of the role of vulnerable plaque in the causation of coronary events, coupled with novel diagnostic and therapeutic approaches, create a new opportunity for progress against cardiovascular disease. The recognition that non-flow-limiting plaques often produce cardiac events has led to the development of invasive and non-invasive methods to identify such plaques prospectively. Treatments such as stenting, photodynamic therapy, and novel pharmaceutical agents are under consideration as methods to stabilize the vulnerable plaques and patients that might be detected, thereby enhancing both primary and secondary prevention. Despite the promise of the field, many issues remain to be resolved, including the focality versus systemic nature of the atherosclerotic process, the ability of detectors to identify the target for which they were developed and prove that such a target is linked to clinical events, and the efficacy of specific therapy. If vulnerable plaques and patients can be successfully identified and treated, there will be immense clinical benefits, accompanied by cost savings.