Administration of high concentrations of oxygen (hyperoxia) is a mainstay of supportive treatment for patients suffering from severe respiratory failure. However, hyperoxia, by generating excess systemic reactive oxygen species (ROS), can exacerbate organ failure by causing cellular injury. Therefore, a better understanding of the signal transduction pathways in hyperoxia may provide the basis for effective therapeutic interventions. The major biological effects of hyperoxia include cell death, induction of stress responses, inflammation, and modulation of cell growth. Major signaling pathways that appear to be involved include the mitogen-activated protein kinases (MAPKs), AP-1, and NF-kappa B, which converge, ultimately, to the expression of a range of stress response genes, cytokines, and growth factors.