One of the common features of several experimental models of neurodegenerative disorders and animal models of toxic exposure to metals is oxidative/nitrosative stress (OS/NS), defined as a series of deleterious events involving the primary formation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). These compounds affect both the structure and function of different biological molecules, leading to toxic events that compromise the redox status. The role of free radical-mediated oxidative damage has been often supported in experimental models of Alzheimer’s disease, Parkinson’s disease and Huntington’s disease, among others, as well as in metal- and metalloid-induced models of neurotoxicity such as those produced by arsenic, and methylmercury. In this review, we summarize the general features of the neurotoxic patterns produced after exposure to different toxins currently employed in animal models of neurodegenerative disorders, i.e. β-amyloid peptide,1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and quinolinic acid, as well as the brain damaging effects of environmental pollutants  such as arsenic and methylmercury. Although free radical formation in all these neurotoxic paradigms has been largely demonstrated, it remains unclear whether neuronal damage is the result of OS/NS, or merely a consequence of other mechanisms independent of ROS and RNS formation. In light of the most recent findings reported in the literature concerning OS/NS and neurotoxicity in these models, we focus our attention on those factors triggering cellular and molecular toxic cascades. In addition, we provide an approach to some promising and novel antioxidant strategies to prevent the alterations produced in these models.