Cellular redox homeostasis is the first line of defense against diverse stimuli and is crucial for various biological processes. Reactive oxygen species (ROS), byproducts of numerous cellular events, may serve in turn as signaling molecules to regulate cellular processes such as proliferation, differentiation, and apoptosis. However, when overproduced ROS fail to be scavenged by the antioxidant system, they may damage cellular components, giving rise to senescent, degenerative, or fatal lesions in cells. Accordingly, this review not only covers general mechanisms of ROS production under different conditions, but also focuses on various types of ROS-involved diseases, including atherosclerosis, ischemia/reperfusion injury, diabetes mellitus, neurodegenerative diseases, and cancer. In addition, potentially therapeutic agents and approaches are reviewed in a relatively comprehensive manner. However, due to the complexity of ROS and their cellular impacts, we believe that the goal to design more effective approaches or agents may require a better understanding of mechanisms of ROS production, particularly their multifaceted impacts in disease at biochemical, molecular, genetic, and epigenetic levels. Thus, it requires additional tools of omics in systems biology to achieve such a goal. Antioxid. Redox Signal. 15, 2867–2908.
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