Publisher Summary This chapter discusses the role of microglial chemokines and chemokine receptors in central nervous system (CNS) inflammation. Microglia are invariably activated during CNS pathology and expresses macrophage-specific surface markers. Microglia contribution to the synthesis of chemokines in the CNS during pathological conditions has also been presented in this chapter. Microglia, therefore, are a substantial part of the chemokinergic network within the CNS. Since most of the endogenous cells of the CNS express receptors for chemokines, a broad spectrum of chemokines in CNS physiology and pathophysiology has been proposed. Chemokines are most likely involved in development and patterning of the brain. Furthermore, chemokines may contribute to CNS synaptic transmission and plasticity. Chemokine signaling in the CNS is involved in physiological as well as pathological processes. Since the scope of functions of chemokines and their receptors has broadened considerably to extend beyond leukocyte-chemoattraction, microglial chemokines, and chemokine receptors might be important factors in controlling the activity of microglia. The identification of the precise relationship of chemokines and microglial activity and the determination, whether microglial activation induced by chemokines will have protective or pathogenic consequences, will be the future challenge.