Fractional flow reserve (FFR), an invasive pressure-derived index of stenosis severity, can be performed easily, rapidly, and safely in patients with coronary artery disease as a surrogate of non-invasive detection of ischemia. Over the last decades, profound clinical and scientific evaluation has demonstrated that FFR is one of the few diagnostic modalities that improve patient outcome and, at the same time, are cost-effective and cost-saving. The increasing use of PCI to treat multivessel disease and complex anatomical subsets has created new demands for accurate, "per stenosis" assessment, since revascularisation should be performed only in those stenosis that are ischaemia generating. Recent studies have demonstrated that this attitude results in better patient outcomes. Altogether, current evidence clearly supports the measurement of FFR in catheterization laboratories in order to provide objective and complementary data to coronary angiography. The purpose of this review is to discuss the value of FFR in the diagnosis and treatment of patients with different anatomical subsets, including intermediate stenosis, multivessel disease, left main disease, serial stenosis, ostial and bifurcation lesions, saphenous vein graft disease and in-stent restenosis, as well as in those presenting with acute coronary syndromes.