Epicardial structural coronary disease remains a principal mechanism of ischemia in chronic coronary syndromes. This article provides key definitions and summarizes the pathobiologic continuum from diffuse plaque burden to focal flow-limiting stenosis, highlighting why angiographic severity alone is an imperfect surrogate of ischemic potential. We then review contemporary invasive physiologic assessment of epicardial disease, including hyperemic and non-hyperemic pressure indices, pullback mapping to distinguish focal versus diffuse patterns, and the potential role of post-percutaneous coronary intervention (PCI) physiology in detecting residual flow limitation and guiding optimization. Integrating anatomy and physiology is essential for individualized management and physiologically meaningful revascularization.