Microglia are the resident immune cells of the brain, deriving from yolk sac progenitors that populate the brain parenchyma during development. During development and homeostasis, microglia play critical roles in synaptogenesis and synaptic plasticity, in addition to their primary role as immune sentinels. In aging and neurodegenerative diseases generally, and Alzheimer’s disease (AD) specifically, microglial function is altered in ways that significantly diverge from their homeostatic state, inducing a more detrimental inflammatory environment. In this review, we discuss the receptors, signaling, regulation and gene expression patterns of microglia that mediate their phenotype and function contributing to the inflammatory milieu of the AD brain, as well as strategies that target microglia to ameliorate the onset, progression and symptoms of AD.