The chemokine network, comprising cell surface G protein-coupled receptors and soluble small molecular-weight protein ligands, constitutes a highly evolved system that facilitates leukocyte recruitment in both innate and adaptive immunity. As such, it has attracted attention from the research community as a means of modulating the immune system, a hypothesis that it appears has already been tested rigorously by microbes during coevolution. Several examples exist to support the notion that viruses, protozoa, and helminths have derived strategies of either exploitation or subversion, for example, using the chemokine network to gain cellular entry or to evade host immune surveillance. It is anticipated that, in the coming years, close examination of the mechanisms underlying these processes should provide opportunities for the generation of novel therapeutics. These may be of use to both thwart the microbial defense strategies and also to treat a variety of inflammatory diseases in which the inappropriate or excessive production of chemokines is pathologically implicated.