With increasing research on vulnerable plaques and uncertainty regarding which lesions require revascularization, the goal of this review is to clarify the indications for percutaneous coronary intervention and discuss which lesions do not warrant treatment by intervention. This paper also briefly reviews the potential advantages and limitations of technology that may enable detection of atherosclerotic plaques that are prone to rupture and discusses the future utility of these technologies in prevention of acute coronary syndromes. Providing an evidence-based understanding of lesion morphology and clinical variables that influence outcome enables the interventional cardiologist to determine which atherosclerotic plaques require PCI.