Biology has revealed that form follows function or function creates the organ. Translating this law at the cellular level, we may say that the ultrastructure follows function or function creates the ultrastructure. The vascular endothelium is an accurate illustration of this rule due to its numerous and many-sided functions carried out by highly specialised cells, structurally equipped for their tasks. Occupying a strategic position between the blood and tissues, the endothelial cell (EC) tightly monitors the transport of plasma molecules, employing bidirectional receptor-mediated and receptor-independent transcytosis and endocytosis, regulates the vascular tone, synthesises and secretes a large variety of factors, and is implicated in the regulation of cell cholesterol, lipid homeostasis, signal transduction, immunity, inflammation and haemostasis. Ultrastructurally, besides the common set of organelles, the characteristic features of the ECs are the particularly high number of vesicles (caveolae) endowed with numerous receptors, transendothelial channels, the specialised plasma membrane microdomains of distinct chemistry, and characteristic intercellular junctions. In addition, by virtue of their number (-6 x 10(13)), aggregated mass (-1 kg), large surface area (-7,000 m2) and distribution throughout the body, the ECs can perform all the assumed functions. The vascular endothelium, with its broad spectrum of paracrine, endocrine and autocrine functions, can be regarded as a multifunctional organ and chief governor of body homeostasis. The ECs exists in a high-risk position. The cells react progressively to aggressive factors, at first by modulation of the constitutive functions (permeability, synthesis), followed by EC dysfunction (loss, impairment or new functions); if the insults persist (in time or intensity), cell damage and death ultimately occur. In conclusion, the ECs are daring cells that have the functional-structural attributes to adapt to the ever-changing surrounding milieu, to use innate mechanisms to confront and defend against insults and to monitor and maintain the body's homeostasis.