Primary Sjögren's syndrome (pSS) is characterized by mononuclear inflammatory infiltrates and IgG plasma cells in salivary and lacrimal glands which lead to irreversible destruction of the glandular tissue and is accompanied by sensation of dryness of mouth and eyes. B cells play a central role in the immunopathogenesis and exhibit signs of hyperactivity. Hyperactivity of B cells is the consequence of the coordinated and integrated action of stimulation of the B-cell receptor, CD40 and toll-like receptors in the presence of appropriate cytokines. As discussed, overexpression of type I IFN and BAFF on one hand and IL-6 and IL-21 on the other hand are critically involved in the enhanced plasma cell formation in pSS patients. Hyperactivity of B cells results in secretion of autoantibodies and production of various cytokines. These insights in the role of B cells in the pathogenetic process of pSS offer ample targets for successful therapeutical intervention in pSS.