The development of quantitative angiography and the introduction of new techniques of intracoronary imaging cannot replace the functional methods for the assessment of stenosis severity. The measurement of the trans-stenotic pressure gradient and of the post-stenotic flow velocity using miniaturized sensors with guidewire technology offers an alternative to the conventional non-invasive methods which is applicable in the catheterization laboratory at the time of the interventional procedure. The complexity of the coronary circulation, however, limits the possibility of establishing simple cut-off criteria to identify the presence of a flow-limiting stenosis. For intermediate lesions, or in the presence of variable haemodynamic conditions, the accuracy of the assessment can be improved by the application of more complex indices, proposed and validated in the animal laboratory and based on the instantaneous relationship between pressure or pressure gradient and flow velocity.