Pressure-derived fractional flow reserve (FFR) is an index of the haemodynamic significance of a coronary lesion. Numerous studies have provided robust evidence that FFR-guided percutaneous coronary intervention is associated with better clinical outcomes and reduces the need for repeat revascularisation. Although FFR is regarded as the gold standard for assessing lesion severity, it has limited clinical applications, mainly because it is a relatively expensive and time-consuming procedure. To overcome these limitations, several computational-based methodologies have been developed which enable estimation of the FFR in three-dimensional models derived from anatomic imaging data. Multislice computed tomographic coronary angiography and quantitative coronary angiography have been proposed for coronary reconstruction and computational evaluation of the FFR. In this review article, we describe the currently available methodologies for the computational estimation of FFR, present evidence derived from their clinical evaluations, stress their limitations, and discuss their potential value in clinical practice.