The diatomic molecule of oxygen contains two uncoupled electrons and can therefore undergo reduction, yielding several different oxygen metabolites, which are collectively called Reactive Oxygen Species or ROS. They are invariably produced in aerobic environments through a variety of mechanisms, which include electron “leakage” during biologic oxidations, action of flavin dehydrogenases and specific membrane associated secretion, as well as by physical activation of oxygen by irradiation, e.g. UV sun-light. Organisms have developed efficient protective mechanisms against excessive accumulation of ROS, which include superoxide anion, hydrogen peroxide and hydroxyl radical, since all these metabolites are highly reactive and affect almost every kind of organism, either directly or through conversion into other derivatives, notably NO-derived radicals or RNS. Depending on their tissue concentration they can either exert beneficial physiologic effects (control of gene expression and mitogenesis) or damage cell structures, including lipids and membranes, proteins and nucleic acids, leading to cell death. In this brief overview we summarize the present state-of-theart, restricting the discussion to the role of ROS in physiology and pathology, not taking into account RNS. Discussion will focus on basic chemical and biochemical features of ROS, underlining how ROS can promote severe diseases, including neoplastic, cardiovascular and neurodegenerative diseases. This brief discussion should clarify the present huge interest in ROS, in the perspective to develop new and specific therapeutic approaches.