The assessment of coronary flow reserve (CFR) may be useful for the functional evaluation of coronary artery disease (CAD). Invasive techniques, such as intracoronary Doppler ultrasound and pressure-derived method, directly assess CFR velocity and fractional flow reserve. Positron emission tomography (PET) has emerged as an accurate noninvasive technique to quantify CFR. Nevertheless, this approach has not been applied to routine studies because of its high cost and complexity. Recently, attempts to estimate CFR with single-photon emission computed tomography (SPECT) tracers have been made in order to obtain, with noninvasive methods, data for quantitative functional assessment of CAD. This review analyzes the relative merit and limitations of CFR measurements by cardiac imaging techniques and describes the potential clinical applications.