Intravascular imaging-derived physiology is emerging as a promising tool allowing simultaneous anatomic and functional lesion assessment. Recently, several optical coherence tomography-based and intravascular ultrasound-based fractional flow reserve (FFR) indices have been developed that compute FFR through computational fluid dynamics, fluid dynamics equations, or machine-learning methods. This review aims to provide an overview of the currently available intravascular imaging-based physiologic indices, their diagnostic performance, and clinical application.