Oxidative stress is a major feature and one of the earliest changes in Alzheimer's disease. The complex nature and genesis of oxidative damage in Alzheimer's disease can be partly answered by mitochondrial and redox-active metal abnormalities. Evidence indicates that in the initial phase of Alzheimer's disease development, amyloid-beta deposition and hyperphosphorylated tau, hallmarks of the disease, are consequences of oxidative stress. Therefore, the authors propose that oxidative modifications in early stages of Alzheimer's disease may actually serve as a homeostatic response or compensatory mechanism against stressful agents resulting in a shift of neuronal priority from normal function to basic survival. Since the cause of Alzheimer's disease pathophysiology remains controversial, several and distinct therapeutic strategies have been tried to avoid, or at least reduce, the development of this neurodegenerative disorder. In this line, the inherent theoretical limitations of secretase inhibitors and immunotherapy, aimed to avoid the production or clear amyloid-beta from the brain is discussed. Promising antioxidant strategies, with the focus on fighting oxidative stress, are highlighted. Currently, antioxidant strategies appear to be the most encouraging therapeutics in reducing the clinical manifestation and evolution of Alzheimer's disease.