Coronary microvascular function and cardiac function are closely related in that proper cardiac function requires adequate oxygen delivery through the coronary microvasculature. Insufficient oxygen supply contributes to development and progression of heart failure. Furthermore, endothelium-derived factors directly modulate cardiac function, and hence endothelial dysfunction may directly impact cardiac function. Risk factors like (pulmonary) hypertension, diabetes and/or hypercholesterolemia directly affect the coronary microvasculature. Evidence is accumulating that the myocardial oxygen balance is disturbed in the failing heart due to increased extravascular compressive forces and coronary microvascular dysfunction. Importantly, coronary microvascular dysfunction is associated with adverse cardiovascular events. Since alterations in microvascular as well as cardiac function are first revealed during increased physical activity, exercise testing provides a valuable method to interrogate coronary microvascular function. Identification of abnormal microvascular responses, i.e. alterations in neurohumoral influences, endothelial dysfunction and oxidative stress, may provide novel targets for therapeutic interventions that improve microvascular function and thereby delay progression of ventricular dysfunction to overt heart failure.