Metal ions have long been linked to the etiology of Alzheimer's disease (AD) via a variety of mechanisms that mainly contribute to a worsening of the pathology. The present chapter proposes a state-of-the-art perspective about the toxic paths related to metal ions, mainly copper and zinc. Copper and zinc that are exchanged within the synaptic cleft can bind to the amyloid-β (Aβ) peptides, a key player in AD. This interaction has two main fallouts: the modulation of the self-assembly ability of the Aβ peptide leading to the formation of amyloid deposits and the production of reactive oxygen species contributing to the overall oxidative stress detected in AD. The molecular basis of these two main toxicity pathways will be described as well as their interrelation and their link with other factors.