Introduction: Alzheimer disease (AD) is the most common age-related neurodegenerative disease characterized by extracellular amyloid-β (Aβ) plaques and intracellular neurofibrillary tangles containing hyper-phosphorylated tau. As an important molecule in the pathogenesis of AD, Aβ interferes with multiple aspects of mitochondrial function, including energy metabolism failure, production of reactive oxygen species (ROS) and permeability transition pore formation. Recent studies have demonstrated that Aβ progressively accumulates within mitochondrial matrix and provides a direct link to mitochondrial toxicity. Convincing evidence demonstrates mitochondria as a crucial organel in ROS generation and links oxidative stress to the development of neuronal dysfunction and death, which suggests a key pathogenic role for oxidative stress in AD. In this review, we focus on changes in mitochondrial defects and oxidative stress in the pathogenesis of AD. Interaction of AD with Aβ exaggerates Aβ-mediated mitochondrial and neuronal perturbation, leading to impaired synaptic function and memory. Conclusion: Blockade of ROS generation may be a potential therapeutic strategy for treatment of AD.