Age-related androgen depletion has been implicated in compromised neuroprotection and is involved in the pathogenesis of neurodegenerative disease, including Alzheimer's disease (AD), the leading cause of dementia. Emerging data revealed that reduction of both serum and brain androgen levels in males is associated with increased amyloid-β (Aβ) accumulation, a putative cause of AD. It has been demonstrated that androgens can function as the endogenous negative regulators of Aβ. However, the mechanisms by which androgens regulate Aβ production, degradation, and clearance, as well as the Aβ-induced pathological process in AD, are still elusive. This review emphasizes the contributions of androgen to Aβ metabolism and toxicity in AD and thus may provide novel strategies for prevention and therapeutics.