Over the last years it has become evident that endothelium is one of the most active paracrine organs releasing a number of vasoactive substances. These mediators, by acting on subjacent vascular smooth muscle, play and important role in control of vasomotor tone and of platelets aggregation. The relations between vascular endothelium and cardiovascular risk factors are complex. Functional abnormalities of vascular endothelium are probably segmental and may differ in individual cases. Experimental and clinical study has demonstrated that all cardiac endothelial cells, coronary vascular and endocardial, modulate the performance of underlying myocardium. Modulation of the left ventricular function by endothelial cells constitutes an important autoregulation of muscle-pump performance of the heart by altering the duration of contraction and diastolic function. It is likely that cardiac endothelial cells take part in extrinsic and intrinsic cardiac compensatory mechanisms and, although there is still no direct evidence, they may be closely involved in pathophysiology of heart failure in humans.