The role of emotional distress (e.g., anger, depression, and anxiety) in anginal chest discomfort (ACD) may have been underestimated. The authors review the empirical studies in this area, which are inconsistent with the standard theory on the ischemia-angina relationship; summarize the substantial evidence indicating a strong and consistent cross-sectional/prospective epidemiological association of emotional distress and ischemia/ACD; review the distress-targeted, interventional evidence confirming a causal relationship (i.e., reduced chest discomfort and health system utilization), thus confirming clinical utility of such interventions; and explore the possible mechanisms that might account for the relationship between emotional distress and chest discomfort. Substantial clinical benefit may be achieved by aggressively detecting and treating emotional distress in ACD patients.