The majority of deaths amongst critically ill patients requiring intensive care are attributable to sepsis and its sequelae: septic shock, the systemic inflammatory response syndrome (SIRS) and the acute respiratory distress syndrome (ARDS). Clinically, sepsis/SIRS and ARDS are characterised by disordered vascular control, manifest as systemic hypotension and peripheral vasodilation refractory to intravascular volume resuscitation and vasopressor therapy; and pulmonary hypertension. Experimental and clinical evidence demonstrates that these patients suffer from severe oxidative stress. Thus, our own and other groups have shown that the vascular pathology of sepsis/SIRS and ARDS is initiated through the uncontrolled production of reactive oxygen (ROS) and reactive nitrogen species (RNS) which modulate inflammatory cell adhesion and cause direct injury to endothelium (Fig. 1).