The routine use of sensor-tipped guide wires for the assessment of functional coronary lesion severity has become widespread in the catheterization laboratory. The physiological parameters derived from pressure or flow velocity measurements, fractional flow reserve, relative and absolute coronary blood flow velocity reserve show a high agreement with noninvasive stress testing for myocardial ischemia. However, since these parameters are based on either intracoronary pressure or flow velocity, they do not investigate the hemodynamics of the coronary circulation completely, leading to ambiguous or conflicting outcomes. Only the use of simultaneously measured distal pressure and flow velocity will avoid any possible misinterpretation of the data. We have successfully used an index of stenosis resistance during maximal hyperemia to characterize the functional significance of a coronary stenosis. Recent developments in guide wire technology, currently used for research investigations, put these simultaneous measurements within clinical reach.