Microglia are the resident tissue macrophages of the central nervous system (CNS) parenchyma and are key players in the initiation of an inflammatory response. Microglia rapidly transform from a resting to an activated morphology in response to a variety of disease states. However, they can also be the target of infections, as in the case of HIV. Many of the effector properties of microglia can be attributed to the array of substances they secrete in response to stimuli such as bacterial lipopolysaccharide, cytokines, and chemokines. The products of activated microglia include: cytokines (pro- and anti-inflammatory), chemokines, nitric oxide, superoxide radicals, and proteases. Furthermore, microglia have the ability to present antigen to T cells, migrate in response to chemotactic stimuli, and phagocytose cell debris. This report focuses on the immunomodulatory functions of microglia, with particular attention to chemokines, and highlights their pivotal role in the CNS.