Over 3 decades, invasive coronary physiology has evolved into a cornerstone of cardiovascular care. Fractional flow reserve (FFR) enabled lesion-specific assessment of epicardial stenoses, improving percutaneous coronary intervention (PCI) selection beyond angiography. Recognition of ischemia without obstructive disease expanded its role, with contemporary testing integrating adenosine-based flow assessment and acetylcholine-based evaluation of endothelial and vasomotor function, allowing identification of angina with nonobstructive coronary arteries endotypes, and tailored therapy. Physiologic pullback and post-PCI indices support procedural planning. Emerging tools, including angiography-derived indices, FFR-computed tomography, and optical coherence tomography (OCT)-based virtual flow reserve, are extending physiology-guided care toward noninvasive assessment and precision cardiovascular intervention.