Publisher Summary This chapter focuses on the expression of chemokine receptors along the brain microvasculature, and their potential role in neuroinflammatory and neuroinfectious processes. The unique properties of the cerebral microvasculature might significantly dictate the course and extent of chemokine action within the central nervous system (CNS), and critically modulate both physiologic and pathophysiologic processes. In numerous inflammatory, traumatic, and infectious conditions of the CNS, astrocytes and infiltrating leukocytes have been determined to be major sources of chemokine production. Chemokine receptors have been reported to be expressed by endothelial cells from a wide variety of tissues and implicated in mediating several aspects of angiogenesis and angiostasis. Such expression by endothelial cells prompts consideration that specialized interactions of chemokines with the brain microvascular endothelium might constitute the incipient steps in directing leukocyte traffic into the CNS. Bilateral expression of chemokine binding sites along both abluminal and luminal surfaces of brain in vivo, may carry important implications for both chemokine and pathogen transport across the blood–brain barrier (BBB). Additional studies have attested to the functional competence of these chemokine binding sites. Confirmation of a role for chemokine receptors at the BBB will expand the endothelium as a target for therapeutics in the treatment of inflammatory, infectious and vascular diseases of the brain.