Chemokines are a superfamily of proteins that play a central role in immune and inflammatory reactions and in viral infections. About 50 different chemokines divided in four subfamilies are known, CXC, CC, C, and CX3C. Chemokine receptors can function as entry/fusion co-receptors for human immunodeficiency virus (HIV)-1 infection, and regulation of receptor expression by cytokines may be relevant for viral infection. Posttranslational processing of chemokines can profoundly affect their interaction with receptors. The serine protease CD26/dipeptidyl-peptidase IV (CD26/DPP IV) removes NH2-terminal dipeptides from several chemokines and profoundly affect their biological activity. Kaposi's sarcoma (KS)-associated herpes virus 8 encodes for three chemokine-like proteins that show homology with MIP cluster of CC chemokines. These viral chemokines possess a partial agonist activity for certain chemokine receptors and may function as receptor antagonists. This biological activity could represent a strategy developed by the virus to subvert immunity impairing the generation of an effective anti-viral immune response.