In the past, the endothelium was considered to be inert, described as a ‘layer of nucleated cellophane’, with only non‐reactive barrier properties, such as presentation of a non‐thrombogenic surface for blood flow and guarding against pro‐inflammatory insults. However, it is now becoming clear that endothelial cells actively and reactively participate in haemostasis and immune and inflammatory reactions. They regulate vascular tone via production of nitric oxide, endothelin and prostaglandins and are involved in the manifestations of atherogenesis, autoimmune diseases and infectious processes. They produce and react to various cytokines and adhesion molecules and it is now clear that they can mount anti‐ and pro‐inflammatory and protective responses depending on environmental conditions and are key immunoreactive cells. Endothelial dysfunction or activation also contributes to a variety of disease states.