The risk of late stent thrombosis represents a major concern for patients treated with drug-eluting stents (DES). Delayed healing and incomplete stent coverage were commonly observed in pathologic specimens of vessels treated with DES. In-situ assessment of the stent coverage has been limited by the low spatial resolution of current image modalities. Optical coherence tomography (OCT) enables real-time, full tomographic, in-vivo visualization of coronary vessel microstructure. Struts coverage and vessel response of DES compared to BMS are the most immediate clinical applications of OCT. Thickness of coverage and strut apposition can be quantified at micron-scale level with a resolution 10-30 times higher than conventional intravascular ultrasound. Current clinical experience demonstrates the high level of accuracy of OCT in evaluating the heterogeneity of vascular healing following DES implantation. Neointimal coverage at strut level assessed by OCT seems a reasonable intermediate endpoint to quickly scrutinize in preregistration studies the safety profile of the next generation of DES. Major limitations of current OCT technology are shallow depth of light penetration and the need to occlude the vessel for blood removal. Second generation forms of OCT, which allow images to be recorded faster (congruent with 10 times) during a nonocclusive flush, have been recently developed. Full, quick scan of multiple and long stent without occlusion balloon is possible. Further technical advancements are expected to provide sharper images with additional contrast and tissue texture characterization. The value of these improvements must be gauged by the degree of impact in DES technology and patient care. (c) 2008 Wiley-Liss, Inc.