Chemokines are now recognized as critical regulators of leukocyte trafficking into the CNS. This leads to the inevitable questions, which cells are producing chemokines and how is this controlled? Numerous studies have revealed that resident cell populations of the CNS are able to synthesize and secrete a variety of chemokines. Astrocytes and microglia are the primary source of chemokines following infection with a wide range of neurotropic viruses, including the JHM strain of mouse hepatitis virus (JHMV), lymphocytic choriomeningitis virus (LCMV), Theiler's murine encephalitis virus (TMEV), herpes simplex virus 1 (HSV1), and human immunodeficiency virus (HIV) [1] [2] [3] [4] . Neurons are also capable of secreting chemokines during HIV and West Nile virus (WNV) infection [5, 6] , while endothelial cells express chemokines during simian immunodeficiency virus-induced encephalitis [7] . Both in vitro and in vivo studies have highlighted that CNS viral infection often results in distinct chemokine signature patterns. For example, Prehaud and colleagues have demonstrated that in vitro infection of neurons with rabies virus (RABV) results in robust production of chemokines, whereas HSV-1-infected neurons do not [8] . However, specific chemokines, e.g., CXCL10 and CCL5, are often expressed independently of either cellular tropism or viral genetics, suggesting that factor(s) either secreted in response to infection (such as type I interferon [IFN]) or utilized for viral recognition are shared between many neurotropic viruses. Tolllike receptors (TLRs) recognize both DNA and RNA and they are able to rapidly respond to viral infection, in part, by promoting chemokine gene expression. During TMEV infection, TLR2 and TLR3 cooperation leads to the expression of the macrophage chemoattractants CCL2 and CCL5 [3] , while TLR2 and TLR9 mediate chemokine expression during HSV-1 infection [4, 9] . Type I IFNs regulate glial-derived chemokine expression in response to CNS infection with LCMV (Traub strain) and HSV-1 [2, 9] ; however, this pathway is dispensable for expression of other chemokines, e.g., CCL2 following infection with JMHV [10] . Rather, JHMV viral proteins influence chemokine secretion through as yet undefined mechanisms [11] , while the HIV-1 protein Nef influences neuronal chemokine secretion [5] . Moreover, WNV-infected cerebellar granule cell neurons readily secrete CXCL10 in vitro, while CXCL10 expression by WNV-infected cortical neurons is muted [12] . The consequence of this differential expression of CXCL10 is reflected in altered migration of defined inflammatory cells into the cerebellum at the expense of other WNV-infected CNS regions [12] . Collectively, these data illustrate that viral infection of the CNS by a wide variety of neurotropic viruses induces highly orchestrated and individual patterns of chemokine secretion by resident cells of the CNS, evoked by disparate pathways that converge into often overlapping profiles of inflammatory cell infiltration.