Alzheimer disease (AD) is a progressive neurodegenerative disease characterized by pathophysiological changes that start years before the onset of cognitive decline. First observed by Alois Alzheimer in 1906, symptomatic AD is characterized by extracellular amyloid-beta (Aβ) plaques, intracellular neurofibrillary tau tangles, and neurodegeneration within the brain in conjunction with cognitive decline. In addition to the traditional hallmark signs, mitochondrial dysfunction occurs in the brain at the earliest stages of disease progression and is also apparent in the peripheral cells and tissues of patients with AD. This review examines the role of mitochondria in AD and the specific alterations that have been described in the literature. Furthermore, evidence is reviewed for mitochondrial dysfunction across various cell types and tissues and insights provided into the factors that can drive systemic bioenergetic decline in AD.