Chemokines are small chemoattractant cytokines involved in cell trafficking and activation. Despite the general nonspecific nature of chemokine activity in certain instances, specific chemokine expression patterns have been associated with specific disease states. In the field of respiratory viral infection, evidence suggests that response to viral invasion is regulated by a distinct chemokine expression profile involving more CC chemokines than CXC chemokines. Moreover, among the CC chemokines, CCL3 and CCL5 appear to be most commonly implicated in viral respiratory disease. Most data available in this field have been derived from in vitro studies, as well as studies conducted in animal models with limited evidence obtained in settings of actual human disease. In the present review, we focus on the diagnostic, prognostic, and therapeutic potential of virus-induced chemokine activity as reflected by studies conducted in actual disease states, either in animal models or humans. We further discuss whether these data advocate chemokines as a realistic clinical tool for the management of viral infection.