Microglia are one of the resident mononuclear phagocyte populations within the central nervous system (CNS). These cells share many phenotypical and functional characteristics with macrophages, suggesting that microglia participate in innate immune responses in the brain. As such, microglia are uniquely poised to provide an initial line of defense against invading pathogens into the CNS prior to peripheral leukocyte infiltration. Numerous studies have shown that microglia are capable of producing a wide array of chemokines that act to initiate or promote inflammatory processes in the CNS through facilitating the recruitment of peripheral immune cells into the CNS parenchyma. In addition, microglia also express numerous chemokine receptors that are involved in cell migration and serve as co-receptors for human immunodeficiency virus-1 (HIV-1) infection. The findings obtained from studies of chemokine expression in animal models of CNS infectious diseases as well as from patient populations highlight a marked promiscuity in cerebral chemokine expression patterns with simultaneous expression of multiple chemokines being the general rule. A detailed discussion regarding the profiles and implications of chemokine and chemokine receptor expression in the context of various CNS infectious diseases including HIV-1 encephalitis, other viral encephalitides, bacterial meningitis, and brain abscess is presented. Future studies dissecting the potential roles of individual chemokines and their receptors in the context of CNS infectious diseases may provide insights into the complex regulatory network dictating neuroinflammatory responses.