Coronary computed tomographic angiography (CT) has emerged as a non-invasive method for direct visualization of coronary artery disease (CAD), with prior studies demonstrating high diagnostic performance of CT compared to an invasive coronary angiography (ICA). However, CT assessment of coronary stenoses tends towards overestimation and even amongst CT-identified severe stenosis confirmed at the time of ICA, only a minority are found to be ischemia-causing. Recent advances in computational fluid dynamics and image-based modeling now permit determination of rest and hyperemic coronary flow and pressure from CT scans-without the need for additional imaging, modification of acquisition protocols, or administration of medications. These techniques have been used to non-invasively compute fractional flow reserve (FFR)- or the ratio of maximal coronary blood flow through a stenotic artery to the blood flow in the hypothetical case that the artery was normal-from CT images. In the recently reported prospective multicenter DISCOVER-FLOW and DeFACTO studies, FFR derived from CT, or FFRCT, was demonstrated as superior to measures of CT stenosis severity for determination of lesion-specific ischemia. Given the significant interest in this novel method for determining the physiologic significance of CAD, we herein present a review on the scientific principles that underlie this technology.