When observed by angioscopy, the culprit lesions of acute coronary syndrome (ACS) have a common appearance of a yellow plaque with irregular surface covered by a thrombus. Angioscopy is a powerful device to detect not only the ruptured plaques at ACS lesions but also the yellow plaques in their early stages. The culprit lesions of ACS are sometimes detected by angioscopy even in the angiographically normal segments of coronary arteries. Angioscopy can further classify the culprit lesions of ACS as (1) vasospasm, (2) plaque rupture, or (3) plaque erosion according to the angioscopic definitions. These classifications may be beneficial to determine the treatment strategy. Anti-vasospastic medications rather than stenting may be more suitable for the treatment of vasospasm-induced ACS. Percutaneous coronary intervention (PCI) of ruptured plaque rather than of erosive plaque tends to cause more distal embolization with thrombus and plaque contents. Therefore, distal protection device may be more beneficial for those cases. Although angioscopy may be able to identify vulnerable plaques as the plaques of intensive yellow color, it may be more practical to identify the patients at high risk of suffering ACS by evaluating the extent of coronary atherosclerosis. The process and the time course of plaque formation, maturation, and disruption are left to be clarified, however, the number of yellow plaques or the yellow color intensity of those plaques may be a marker of coronary atherosclerosis. Angioscopy should be useful not only as a diagnostic tool but also as an investigational tool. The effect of medications that regress coronary atherosclerosis may be evaluated by the angioscopically determined markers of coronary atherosclerosis.