© 2015 The Authors.Coronary intervention is increasingly performed in complex disease with tandem and diffuse disease. Pressure wires enable detailed assessment of the physiological significance of a stenosis but in the presence of tandem disease, predicting the impact of a stenting a given stenosis can be difficult and is impeded by flow interaction between stenoses under hyperemia. In this review, we consider the physiological difficulties posed by flow interaction under hyperemia and consider alternative approaches such as assessment under baseline conditions. Specifically we consider the potential value of the iFR-Pullback approach and its capacity to enable Virtual-PCI, which may assist in planning intervention.