As the importance of the endothelium is becoming increasingly recognised, additional tools are needed to assess its functions. Separate studies have looked at different aspects of vascular biology primarily focusing on the central role of the endothelium, i.e. secretion/release of molecules in the plasma, physiological action on other cells, and the presence of endothelial cells themselves in the circulation. Targeting and protecting the endothelium is a promising therapeutic strategy for modifying a number of disease processes but 'ideal' methods to monitor this treatment, like many other tools for assessing endothelial activity, remain elusive. We suggest that a broader view of the endothelium is important, and with it the concept of the assessment of overall vascular function, which fuses different aspects of endothelial activity into a unifying concept. In the present document we review the current understanding of endothelial biology and the methods of its assessment, and hypothesise that a more multifactorial approach to the endothelium will be a crucial determinant of outcomes and treatment strategies for different diseases. This we describe as the 'endotheliome'.