Despite the exposure of the general population to a wide variety of exogenous environmental toxins, a growing armamentarium of potent medications, and an array of licit and illicit drugs, relatively little evidence of related pathophysiologic effects is seen on the radiographic appearance of the heart. When radiographic changes are manifested, however, specific alterations are observed in the contour of the cardiac silhouette. Generalized enlargement of the cardiac silhouette may be secondary to development of dilated cardiomyopathy or the accumulation of pericardial fluid. Localized changes in the contour of specific portions of the cardiac silhouette may be the result of ventricular hypertrophy or valvular stenosis or regurgitation. This article describes the cardiac radiographic findings resulting from the use of specific substances and discusses possible mechanisms that ultimately result in these changes. Identification and characterization of these morphologic changes may be helpful in the clinical management of patients.