Acute coronary syndromes are a spectrum of clinical presentations with various pathophysiologic substrates. As such, there is not one single type of lesion responsible for stable or unstable angina, acute myocardial infarction, and sudden cardiac death. Most of the information regarding the characteristics of culprit lesions derives from histopathologic studies, whether postmortem or from atherectomy samples, and from studies using angiography, angioscopy, and intravascular ultrasound. Characterization of the unstable coronary lesion is key to understanding the pathophysiology of coronary artery disease, this knowledge will allow clinicians to individualize treatment according to specific lesion types, and more importantly, will lead to strategies to identify atherosclerotic lesions in their early stages and implement preventive therapies.