Since its invention in the late 1990s, intravascular optical coherence tomography (OCT) has been rapidly adopted in clinical research and, more recently, in clinical practice. Given its unprecedented resolution and high image contrast, OCT has been used to visualize plaque characteristics and to evaluate the vascular response to percutaneous coronary intervention. In particular, OCT is becoming the standard modality to evaluate in vivo plaque vulnerability, including the presence of lipid content, thin fibrous cap, or macrophage accumulation. Furthermore, OCT findings after stent implantation, such as strut apposition, neointimal hyperplasia, strut coverage, and neoatherosclerosis, are used as surrogate markers of the vascular response. New applications for OCT are being explored, such as transplant vasculopathy or non-coronary vascular imaging. Although OCT has contributed to cardiovascular research by providing a better understanding of the pathophysiology of coronary artery disease, data linking the images and clinical outcomes are lacking. Prospective data are needed to prove that the use of OCT improves patient outcomes, which is the ultimate goal of any clinical diagnostic tool.