Chemokines represent a family of over 40 small proteins that, for the most part, are secreted into the environment and function by binding to G protein-coupled receptors (GPCRs) that are expressed on numerous different cell types. When initially identified close to 30 years ago, these molecules were associated with various human inflammatory diseases and it was recognized that expression may be integral in leukocyte recruitment to inflamed tissue. Within a relatively short period of time, early participants within the field determined that these proteins displayed distinct and conserved structural features and exerted potent chemotactic effects on defined lymphocyte subsets. There are now four sub-families of chemokines identified based on defined structural criteria relating to the positional location of conserved cysteine residues within the amino-terminus of the protein. Chemokines are now recognized as important in numerous biological processes ranging from maintaining the organizational integrity of secondary lymphoid tissue to participating in various aspects of both innate and adaptive immune responses following microbial infection. The host response to viral infection represents a well-orchestrated ballet consisting of numerous participants with diverse roles in defense but with the ultimate goal of generating virus-specific lymphocytes whose job is to control and eliminate the invading viral pathogen from infected tissues. Over the years, an emerging picture has developed that indicates that chemokines and their receptors are intimately involved in development of effective host responses to viral pathogens. Chemokine expression is now associated with all facets of defenseagainst viral infection including linking innate and adaptive immune responses.