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The assessment of different aspects of endothelial dysfunction in cardiovascular medicine in general and in heart failure (HF) has been the focus of intense research, and includes vasomotor, haemostatic, antioxidant, and inflammatory activities. Differences also exist in the pattern of endothelial dysfunction depending on aetiology, severity, and stability of HF in individual patients. In the majority of patients with ischaemic aetiology of HF, endothelial dysfunction is systemic in its nature and involves both arteries and veins, conductance vessels and microvascular beds, coronary, pulmonary, and peripheral vessels. The pattern of endothelial dysfunction is more heterogeneous in non-ischaemic HF, with fewer features of systemic abnormalities. Indeed, many subjects with non-ischaemic HF have a functionally preserved endothelium in peripheral arteries, with endothelial dysfunction seen only in coronary vessels. Endothelial dysfunction has significant prognostic value in HF, but its clinical application is hampered by methodological limitations in its assessment. Various medications (including angiotensin-converting enzyme inhibitors and statins) and regular physical activity have been shown to improve endothelial function in HF. However, there are still no pharmaceutical agents specifically targeting the vascular endothelium. Despite the large number of studies, the pathophysiological role of the vascular endothelium and its clinical potential as a therapeutic target has not yet been sufficiently developed and undoubtedly awaits further exploration.