While our understanding of vulnerable coronary plaque is still at an early stage, the concept that certain types of plaques predispose patients to developing an acute myocardial infarction continues to be at the forefront of cardiology research. Intracoronary optical coherence tomography (OCT) has been developed to both identify and study these lesions due to its distinct resolution advantage over other imaging modalities. We review clinical research conducted at the Massachusetts General Hospital over the past five years to develop, validate, and utilize this technology to improve our understanding of vulnerable plaque. Our results show that intracoronary OCT may be safely conducted in patients and that it provides abundant information regarding plaque microscopic morphology, which is essential to the identification and study of high-risk lesions. Even though many basic biological, clinical, and technological challenges must be addressed prior to widespread use of this technology, the unique capabilities of OCT ensure that it will have a prominent role in shaping the future of cardiology.