Alzheimer’s disease (AD) is the most common progressive and irreversible neurodegeneration characterized by the impairment of memory and cognition. Despite years of studies, no effective treatment and prevention strategies are available yet. Identifying new AD therapeutic targets is crucial for better elucidating the pathogenesis and establishing a valid treatment of AD. Growing evidence suggests that microglia play a critical role in AD. Microglia are resident macrophages in the central nervous system (CNS), and their core properties supporting main biological functions include surveillance, phagocytosis, and the release of soluble factors. Activated microglia not only directly mediate the central immune response, but also participate in the pathological changes of AD, including amyloid-beta (Aβ) aggregation, tau protein phosphorylation, synaptic dissection, neuron loss, memory function decline, etc. Based on these recent findings, we provide a new framework to summarize the role of microglia in AD memory impairment. This evidence suggests that microglia have the potential to become new targets for AD therapy.