Alzheimer’s disease (AD) is a neurodegenerative disorder that is characterized by progressive loss of basal forebrain cholinergic neurons, leading to reduction in transmission through cholinergic fibers involved in processes of attention, learning, and memory. Mitochondria provide and regulate cellular energy and are crucial for proper neuronal activity and survival. Mitochondrial dysfunction is evident in early stages of AD and is involved in AD pathogenesis. This review focuses on the evidence supporting a clear association between amyloid-β toxicity, mitochondrial dysfunction, oxidative stress and neuronal damage/death in Alzheimer’s disease. To date, the beta amyloid (Aβ) cascade hypothesis still remains the main pathogenetic model of Alzheimer’s disease (AD), but its role in the majority of sporadic AD cases is uncertain. Furthermore, the “mitochondrial cascade hypothesis” could explain many of the biochemical, genetic, and pathological features of sporadic AD. This hypothesis promotes mutations in mitochondrial DNA (mtDNA) as the basis for Alzheimer’s disease. The mutations could lead to energy failure, increased oxidative stress, and accumulation of Aβ, which in a vicious cycle reinforces the mtDNA damage and oxidative stress.