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Purpose of Review: The goal of this review is to offer an updated and comprehensive summary of the available options for performing both invasive and noninvasive functional assessments of coronary artery disease. Recent Findings: Fractional flow reserve (FFR) is an invasive functional coronary assessment of ischemia associated with clinical outcomes. In recent years, alternative pressure wire measurements that do not require hyperemic agents have been developed. Measurements such as instantaneous wave-free ratio (iFR) are non-inferior to FFR, result in shorter procedure times, and eliminate side effects related to the use of vasodilatory agents. With advances in technology and computational fluid dynamics, non-invasive methods based on invasive and non-invasive coronary angiograms have been developed to allow for hyperemia-free and wire-free assessments. Summary: Accurate methods to diagnose clinically significant ischemic heart disease are essential, and these novel systems are safer than they have been in the past. This review offers a comprehensive overview and guidance on best practices in conducting these assessments. Opinion Statement: This review aims to highlight best practices in conducting functional coronary assessments to diagnose clinically significant coronary artery disease. Although coronary angiography is the gold standard for diagnosing coronary artery disease, two-dimensional imaging has limitations. Understanding whether a vessel has an ischemia-causing, physiologically significant obstruction requires additional evaluation beyond a visually-interpreted coronary angiogram. Fractional flow reserve (FFR) has been extensively studied and determined to be an effective tool for clinical decision-making in the approach to revascularization for ischemic heart disease. Instantaneous wave-free ratio (iFR) is another assessment method (not requiring the use of hyperemic agents) that has been directly compared to and proven to be non-inferior to FFR in randomized control trials. Measurements such as the diastolic hyperemia-free ratio (DFR) and the resting full-cycle ratio (RFR) have subsequently been compared to iFR. Analytic software such as FFRangio and Quantitative flow ratio (QFR), which utilize images from invasive coronary angiograms, are growing in popularity as a methodology for evaluating stenoses. There are potential benefits of a reduced procedure time, contrast use, and fluoroscopy time with this strategy. Coronary computed tomography angiography-derived FFR is a non-invasive method of determining the likelihood a stenosis is causing significant ischemia. Discussion with patients of the risks and benefits of all available options is a best practice. Intermediate severity obstructive epicardial stenoses in major epicardial vessels should be further evaluated by physiology in symptomatic or high risk patients. Functional assessments for coronary microvascular disease should be performed in patients with documented ischemia, a history of potentially cardiac symptoms, and lack of obstructive disease. Noninvasive options also diagnose obstructive coronary artery disease with high accuracy. [ABSTRACT FROM AUTHOR]