Microglia, the immune cells of the central nervous system, play a crucial role in Alzheimer's disease (AD). Human genetics data indicate that microglia are highly expressed in AD risk genes, suggesting their involvement in the disease pathogenesis. Microglia can protect against AD by clearing β-amyloid (Aβ) and preventing synapse loss, but they can also be harmful by engaging in synapse engulfment, exacerbating tau pathology, and secreting inflammatory factors. Gene expression profiles reveal multiple states of microglial activation, which may explain their disparate roles in AD. The TREM2 gene, highly expressed in microglia, is particularly important for microglial function and AD risk. Microglial dysfunction, as seen in TREM2-deficient mice, can lead to increased Aβ accumulation and neurodegeneration. Complement activation, mediated by microglia, is implicated in synapse loss and tau pathology, further complicating the role of microglia in AD. Transcriptional profiling of microglia in AD brains shows a disease-associated microglial (DAM) state, which may be protective but can become detrimental as the disease progresses. Understanding the complex roles of microglia in AD is essential for developing effective therapeutic strategies.Microglia, the immune cells of the central nervous system, play a crucial role in Alzheimer's disease (AD). Human genetics data indicate that microglia are highly expressed in AD risk genes, suggesting their involvement in the disease pathogenesis. Microglia can protect against AD by clearing β-amyloid (Aβ) and preventing synapse loss, but they can also be harmful by engaging in synapse engulfment, exacerbating tau pathology, and secreting inflammatory factors. Gene expression profiles reveal multiple states of microglial activation, which may explain their disparate roles in AD. The TREM2 gene, highly expressed in microglia, is particularly important for microglial function and AD risk. Microglial dysfunction, as seen in TREM2-deficient mice, can lead to increased Aβ accumulation and neurodegeneration. Complement activation, mediated by microglia, is implicated in synapse loss and tau pathology, further complicating the role of microglia in AD. Transcriptional profiling of microglia in AD brains shows a disease-associated microglial (DAM) state, which may be protective but can become detrimental as the disease progresses. Understanding the complex roles of microglia in AD is essential for developing effective therapeutic strategies.