In 1919, Pio del Rio-Hortega first described a class of cells residing in the brain with a tiny soma and branched architecture distinguishable from astrocytes and neurons.These cells, called microglia or mesoglia, have come to be appreciated as resident immune cells in the central nervous system (CNS).In the year 2019, we review the three most recent advances in microglia research in this 100th year since their discovery (Fig.1).We first discuss their transcriptional diversity, which allows us to appreciate the heterogeneity of microglia across species, development, diseases, and brain regions.We also highlight recent stem cell-based approaches that allow us to study human microglia.We further review new signaling mechanisms that expand our understanding of how microglia sense synaptic changes and alter neural circuits.Ultimately, 100 years of microglial research demonstrates their incredible adaptation and plasticity, playing roles in neural development, brain homeostasis, and neurological disorders far beyond their anticipated immunological function.