Environmental stressors exert a profound effect on humans. Many environmental stressors have in common the ability to induce reactive oxygen species. The goal of this chapter is to present evidence that the potent lipid mediator platelet-activating factor (PAF) is involved in the effects of many stressors ranging from cigarette smoke to ultraviolet B radiation. These environmental stressors can generate PAF enzymatically as well as PAF-like lipids produced by free radical-mediated attack of glycerophosphocholines. Inasmuch as PAF exerts both acute inflammation and delayed immunosuppressive effects, involvement of the PAF system can provide an explanation for many consequences of environmental stressor exposures.