A pathogenic role for autoantibodies, immune complexes and mast cells has long been hypothesized in rheumatoid arthritis (RA). Recent studies demonstrating novel RA-associated autoantibodies and the efficacy of B cell-directed therapy have led to a renewed interest in the role of humoral immunity in RA. Mouse models of arthritis have provided further support for a direct pathogenic role of autoantibodies in the development of synovial inflammation. Interestingly, in antibody-mediated K/BxN serum transfer arthritis, mast cells have now been identified as a critical cellular mediator of autoantibody-driven joint inflammation. Here, we focus on the role of autoantibodies and mast cells in murine and human inflammatory arthritis.