Chemokines are a highly specialized group of cytokines that coordinate trafficking and homing of leucocytes between bone marrow, lymphoid organs and sites of infection or inflammation. They are also responsible for structural organization within lymphoid organs. Aberrant expression or function of these molecules, or their receptors, has been linked to protection or susceptibility to specific infectious diseases, as well as the risk of autoimmune disease and malignancy, revealing critical roles of chemokines and their receptors in human health, disease and therapeutics. In this review, we focus on human diseases that provide lessons regarding the critical role of these specialized and complex cytokines.