This review examines the role of reactive species RS (of oxygen ROS, nitrogen RNS and halogen RHS) on innate immunity. The importance of these species in innate immunity was first recognized in phagocytes that underwent a "respiratory burst" after activation. The anion superoxide O and hydrogen peroxide HO are detrimental to the microbial population. NADPH oxidase NOx, as an O producer is essential for microbial destruction, and patients lacking this functional oxidase are more susceptible to microbial infections. Reactive nitrogen species RNS (the most important are nitric oxide radical -NO, peroxynitrite ONOO and its derivatives), are also harmful to microorganisms, including bacteria, viruses, and parasites. Hypochlorous acid HOCl and hypothiocyanous acid HOSCN synthesized through the enzyme myeloperoxidase MPO, which catalyzes the reaction between HO and Cl or SCN, are important inorganic bactericidal molecules, effective against a wide range of microbes. This review also discusses the role of antimicrobial peptides AMPs and their induction of ROS. In summary, reactive species RS are the heart of the innate immune system, and they are necessary for microbial lysis in infections that can affect mammals throughout their lives.