CXCR3 is a G protein-coupled, seven-transmembrane receptor that binds and is activated by the three IFN-gamma-inducible chemokines of the CXC family named CXCL9, CXCL10, and CXCL11. These chemokines are not constitutively expressed but are up-regulated in a proinflammatory cytokine milieu. Consequently, their major function is to selectively recruit immune cells at inflammation sites, but they also play a role in angiogenesis mechanisms. In the last few years, strong experimental and clinical evidence has been obtained supporting the idea that the CXCR3 pathway is involved in the development of autoimmune diseases, especially by creating local amplification loops of inflammation in target organs, thereby inducing worsening of clinical manifestations. This article briefly reviews what we know today about the nature and functions of CXCR3, with special emphasis on its involvement in two main rheumatic systemic autoimmune diseases, namely rheumatoid arthritis and systemic lupus erythematosus.