NADPH oxidase–derived ROS have beneficial and deleterious effects. NADPH oxidase–derived ROS have damaging oxidative effects that are important for microbial killing but can damage host tissues. In addition, derivative ROS have immunoregulatory effects, which act to balance immune responses that otherwise promote inflammation and even autoimmunity. Likely factors contributing to abnormal inflammation in the absence of NADPH oxidase ROS include impaired digestion of microbes or debris, increased proinflammatory cytokine production reflecting changes in redox-regulated signals, delayed clearance of inflammatory neutrophils, and altered antigen presentation. Professional illustration by Patrick Lane, ScEYEnce Studios.