4-Hydroxy-2-nonenal (HNE) is one of the major products generated during the peroxidation of n-6 polyunsaturated fatty acids, such as linoleic acid and arachidonic acid, and is believed to be largely responsible for the cytopathological effects observed during oxidative stress. In the past decade, considerable progress has been made toward understanding the chemistry and biology of HNE. We now know how abundantly HNE can be generated during lipid peroxidation in vitro and in vivo and how reactive HNE is, especially toward proteins. We also know that the protein-bound HNE could serve as a ligand for a scavenger receptor and function as an immunological trigger for cell signalling and for the production of anti-DNA autoantibodies in autoimmune diseases. These findings strongly suggest that HNE can be causally involved in many of the pathophysiological effects associated with oxidative stress in cells and tissues. In this special meeting, I will give a brief overview on the current status of HNE, focusing mainly on its protein adducts.