The pressure wire has revolutionised cardiology by moving the focus of revascularisation from anatomy to physiology. This review provides a comprehensive viewpoint on the foundations of the field of intracoronary physiology, with emphasis on the development and clinical evidence of fractional flow reserve (FFR). Additionally, we critically appraise clinical decision making based on the evolving area of resting coronary physiology. The emerging role of coronary flow reserve and its complementariness with FFR is also discussed, and the importance of the invasive assessment of the coronary microcirculation in outlining prognosis is put into perspective. Overall, this review summarises the capacity of invasive coronary physiology indices to guide revascularisation and to discriminate patients at high risk of an adverse cardiovascular outcome.