Decisions regarding coronary interventions should be combined with objective evidence of myocardial ischemia. The most common physiologic approach utilizes hospital facilities outside the catheterization laboratory, requiring additional time and cost. With the introduction of sensor-tipped angioplasty guide wires, distal coronary flow velocity and pressure can be obtained in the cardiac catheterization laboratory, facilitating physiologically based decisions regarding the need for intervention. In the catheterization laboratory, physiologically significant stenoses can be characterized as having impaired post-stenotic coronary flow reserve <2.0 and pressure-derived fractional flow reserve <0.75, both variables related strongly to positive ischemic perfusion imaging or stress testing results. Deferring coronary interventions on the basis of normal translesional physiology is safe and is associated with a low rate (<10%) of lesion progression over a 10-month follow-up period. Preliminary data indicate that excellent physiologic and anatomic end points after balloon angioplasty are associated with low (<20%) restenosis rates at 6-month follow-up. Clinically relevant relations of in-laboratory physiology support the insight that physiologic, as much as or more than anatomic variables, ultimately determine the functional status of a patient. Current data suggest that an intracoronary physiologic approach complements coronary lumenology and appears to have important clinical and economic implications for patients undergoing invasive evaluation and treatment of coronary artery disease.