CXCR5 (also known as BLR1) is a GPCR that binds selectively to the chemokine CXCL13 (also known as BLC and BCA-1) to mediate immune system development and function. CXCR5 cooperates with CCR7 to determine functional organization of lymphoid organs such as lymph nodes and Peyer’s patches. In addition, CXCR5 mediates migration of B cells into the follicles of the splenic white pulp, thus permitting antigen deposition on follicular dendritic cells. Patients with rheumatoid arthritis (RA) displayed upregulated expression of CXCR5 to a greater extent than other chemokine receptors, and CXCR5-null mice subjected to antigen-induced arthritis display reduced joint destruction. Therefore, CXCR5 represents a potential target for treatment of rheumatoid arthritis.