High mobility group box (HMGB)1, originally described as a nuclear protein that binds to and modifies DNA, is now regarded as a central mediator of inflammation by acting as a cytokine. HMGB1 is postulated to be particularly important as a late acting mediator of lethal septicaemia in mice. Furthermore, it has been suggested that HMGB1 plays a role in clinical conditions such as autoimmunity, acute ischaemia-reperfusion injury, cardiovascular disease and cancer. HMGB1 has emerged as a candidate for therapeutic intervention in various disease conditions. However, further basic and clinical studies are warranted to confirm the roles played by HMGB1 in clinical medicine.