The extracellular aggregation of insoluble protein deposits of amyloid-β (Aβ) into plaques and the hyperphosphorylation of the intracellular protein tau leading to neurofibrillary tangles are the main pathological hallmarks of Alzheimer’s disease (AD). Both Aβ and tau are metal-binding proteins. Essential trace metals such as zinc, copper, and iron play important roles in healthy brain function but altered homeostasis and distribution have been linked to neurode- generative diseases and aging. In addition, the presence of non-essential trace metals such as aluminum has been associated with AD. Trace metals and abnor- mal metal metabolism can influence protein aggregation, synaptic signaling path- ways, mitochondrial function, oxidative stress levels, and inflammation, ultimately resulting in synapse dysfunction and neuronal loss in the AD brain. Herein we provide an overview of metals and metal-binding proteins and their pathophysi- ological role in AD.