Microglia, of myeloid origin, play fundamental roles in the control of immune responses and the maintenance of central nervous system homeostasis. These cells, just like peripheral macrophages, may be activated into M1 pro-inflammatory or M2 anti-inflammatory phenotypes by appropriate stimuli. Microglia do not respond in isolation, but form part of complex networks of cells influencing each other. This review addresses the complex interaction of microglia with each cell type in the brain: neurons, astrocytes, cerebrovascular endothelial cells, and oligodendrocytes. We also highlight the participation of microglia in the maintenance of homeostasis in the brain, and their roles in the development and progression of age-related neurodegenerative disorders.