β-arrestins represent a small family of G protein-coupled receptors (GPCRs) regulators, which provide modulating effects by facilitating desensitization and internalization of GPCRs as well as initiating their own signalings. Recent reports have demonstrated that β-arrestins levels were correlated with amyloid-β peptide (Aβ) pathology in brains of Alzheimer's disease (AD) patients and animal models. β-arrestins could enhance the activity of γ-secretase via interacting with anterior pharynx defective 1 subunit, which increased Aβ production and contributed to the pathogenesis of AD. In addition, Aβ-induced internalization of β2-adrenergic receptor internalization and loss of dendritic spine in neurons were proven to be mediated by β-arrestins, further establishing their pathogenic role in AD. More importantly, deletion of β-arrestins markedly attenuated AD pathology, without causing any gross abnormality. Here, we review the evidence about the roles of β-arrestins in the progression of AD. In addition, the established and postulated mechanisms by which β-arrestins mediated in AD pathogenesis are also discussed. Based on the role of β-arrestins in AD pathogenesis, genetically or pharmacologically targeting β-arrestins might provide new opportunities for AD treatment.