There is significant evidence arising from experimental models that autoantibodies play a key role in the pathogenesis of inflammatory arthritis. In addition to autoantibody production, B cells efficiently present antigen to T cells, produce soluble factors, including cytokines and chemokines, and form B cell aggregates in the target organ of rheumatoid arthritis. In this review we analyze the multifaceted role that B cells play in the pathogenesis of rheumatoid arthritis and discuss how this information can be used to guide more specific targeting of B cells for the therapy of this disease.