Purpose of Review The involvement of chemokines and their receptors in the genesis and perpetuation of rheumatoid arthritis, spondyloarthritis, and osteoarthritis has been clearly recognized for a long time. Nevertheless, the complexity of their contribution to these diseases is now becoming evident and this review focuses on published evidence on their mechanism of action. Recent Findings Studies performed on patients and in vivo models have identified a number of chemokine-mediated pathways involved in various aspects of arthritogenic processes. Chemokines promote leukocyte infiltration and activation, angiogenesis, osteoclast differentiation, and synoviocyte proliferation and activation and participate to the generation of pain by regulating the release of neurotransmitters. Summary A number of chemokines are expressed in a timely controlled fashion in the joint during arthropathies, regulating all the aspects of inflammation as well as the equilibrium between damage and repair and between relief and pain. Thus, the targeting of specific chemokine/chemokine receptor interactions is considered a promising tool for therapeutic intervention.