The endocardial endothelium (EE) modulates the performance of the subjacent myocardium and plays an important role in regulation of cardiac function. This modulation has been confirmed in a number of different species and in both in vitro and in vivo conditions. The mechanisms of EE modulation of myocardial performance are still under investigation and the possibilities include the role of EE as a transendothelial physico-chemical barrier and/or the release of various chemical messengers by the EE.