Over the last 15 years, the use of invasive coronary physiology in the catheterization laboratory has demonstrated favorable outcomes for decision making in patients with intermediate single-vessel stenoses, complex bifurcation and ostial branch stenoses, multivessel coronary artery disease, and left main stenoses. A recent large multicenter study (FAME FFR versus Angiography for Multivessel Evaluation) found that a physiologically-guided approach was superior to the standard angiographically-guided approach for percutaneous revascularization in patients with multivessel coronary artery disease. This review addresses selected pertinent concepts and studies supporting the integration of coronary physiology in the catheterization laboratory for optimal patient outcomes.