Reactivespecies participate in normal cellular function orin pathological mechanisms depending on their overproduction. Reactive oxygen species (ROS) and reactive nitrogen species (RNS), are produced through several mechanisms by the cell: the electron transport chain in mitochondria, various cytosolic and membrane enzymes (i.e., xanthine oxidase (XO), nitric oxide synthase (NOS), NADPH oxidase complex, etc.), as well as exogenously provided by the environment. At the same time, cells have several antioxidant defense mechanisms for detoxifying ROS and RNS, including enzymes (i.e., superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and nonenzymatic antioxidants (i.e., reduced glutathione (GSH), vitamins E and C. The main generation pathways of ROS and RNS are also shown: the reduction of O2 occurs by diverse mechanisms (i.e., mitochondria, XO, NADPH-oxidase complex) leading to formation of superoxide anion (O2•-); which is easily transformed to hydrogen peroxide (H2O2) either nonenzymatically or by SOD. H2O2 is converted to H2O by CAT, or by GPx, which together with the GR regenerate GSH. In addition, under stress conditions and high concentration of transition metal (i.e., iron ions—Fe), O2 •- can generate hydroxyl radical (OH•), which in turn can react with polyunsaturated fatty acids (PUFAs) and generate peroxyl radical (ROO•). Finally, O2 •- can react with nitric oxide (NO; depending on NOS), producing the highly reactive peroxinitrite (ONOO•) anion, whereas H2O2 is converted to hypochlorous acid (HOCl) by myeloperoxidase (MPO). The balance between oxidants compounds and antioxidant defense determines the end result. Optimal physiologic levels leads to beneficial effects, with ROS and RNS acting as second messengers in intracellular signaling cascades (modulation of gene regulation and signal transduction pathways, mainly by activation of NFκB), regulating several physiological functions (i.e., cognitive and immune functions). However, when overproduction of ROS/RNS is higher than the antioxidant system, the equilibrium status favors oxidant vs. antioxidant reactions, leading to oxidative stress, in which ROS/RNS have harmful effects, because of their reaction with various macromolecules (lipids, proteins and nucleic acids), contributing to cellular and tissue oxidative damage, and the development of age-related impairments. Oxidation products: 3-NT, 3-nitrotyrosine; 8-OHdG, 8-hydroxy-2-deoxyguanosine; malondialdehyde (MDA); alkoxyl radical (RO•).