Extracellular accumulation of amyloid-β (Aβ) peptide and death of neurons in brain regions involved in learning and memory, particularly the cortex and the hippocampus, are central features of Alzheimer’s disease (AD). Neuronal Ca²⁺ overload and apoptosis are known to occur in AD. Aβ might play a role in disrupting Ca²⁺ homeostasis, and this AD-associated amyloidogenic peptide has been reported to induce apoptotic death in cultured cells. However, the specific intracellular signaling pathways by which Aβ triggers cell death are not yet well defined. This article provides evidence for the involvement of mitochondrial dysfunction in Aβ-induced toxicity and for the role of mitochondria in apoptotsis triggered by Aβ. In addition, the endoplasmic reticulum (ER) seems to play a role in Aβ-induced apoptotic neuronal death, the ER stress being mediated by the perturbation of ER Ca²⁺ homeostasis. It is likely that a better understanding of how Aβ induces neuronal apoptosis will lead to the identification of potential molecular targets for the development of therapies for AD.