A key feature of the immune system is the migration of leukocytes throughout the organism in an effort to patrol for infectious pathogens, tissue damage, and other physiological insults. This remarkable surveillance system is controlled by a family of proteins called chemokines (chemoattractant cytokines), and their respective receptors. Originally discovered because of their role in cell recruitment during inflammation, it is now well recognized that chemokines are also involved in other diverse processes including lymphocyte development and homing, organogenesis, and neuronal communication. While chemokines have evolved largely for host protection, their ability to induce cell damage and inappropriate cell recruitment, can lead to disease. Thus, there is considerable interest in developing antagonists. In this review we emphasize what is known about the structural biology of chemokines, chemokine receptors, and interactions with cell surface glycosaminoglycans. We also briefly describe their role in certain diseases and strategies for interfering with chemokine function that have emerged from mechanistic and structural understanding of their function. Finally we discuss viral mechanisms for sabotaging or manipulating the chemokine system, in part to illustrate the level of molecular mimicry that viruses have achieved and the evolutionary pressure imposed on the immune system by these pathogens.