Chemokines and their receptors play a key role in development and homeostasis as well as in the pathogenesis of tumors and autoimmune diseases. Chemokines are involved in the implantation of the early conceptus, the migration of subsets of cells during embryonic development, and the overall growth of the embryo. Chemokines also have an important role in the development and maintenance of innate and adaptive immunity. In addition, they play a significant role in wound healing and angiogenesis. When the physiological role of chemokines is subverted or chronically amplified, disease often follows. Chemokines are involved in the pathobiology of chronic inflammation, tumorigenesis and metastasis, as well as autoimmune diseases. This article reviews the role of chemokines and their receptors in normal and disease processes and the potential for using chemokine antagonists for appropriate targeted therapy.