Chemokines (CKs) are chemo-attractants that mobilize and activate leukocytes of the immune system. CKs and their receptors have become targets for drug discovery and development on the basis of correlations between their expression profiles and autoimmune diseases. Essential for both physiological immunity and pathological autoimmunity, these immune messengers and regulators have proven to be tantalizing drug targets. Drug inhibitors of disease-related CK receptors adversely affect physiological processes which are unrelated to the targeted disease. We argue that drugs which modulate, rather than negate CK activity, may be the answer to fortuitous and deleterious side effects. CKs, more than their receptors, lend themselves to therapeutic modulation that is disease specific.