Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by chronic inflammation of salivary and lachrymal glands, and frequently accompanied by systemic symptoms. A subgroup of SS patients develops malignant B cell non-Hodgkin's lymphoma (NHL), usually of the mucosa-associated lymphoid tissue (MALT) type and very often located in the major salivary glands. Currently, there is a lack of evidence-based intervention therapy which may influence SS-related chronic inflammation and lymphoproliferation. B cells are involved in the pathogenesis of SS, and B cell downregulation may lead to a decrease of disease activity. Rituximab (RTX), a chimeric monoclonal antibody targeting the CD20 antigen on the B cell surface, has been successfully investigated in other autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, ANCA-associated vasculitis, and mixed cryoglobulinemic syndrome. Preliminary experiences of RTX therapy in SS patients with or without a lymphoproliferative disorder suggest that SS patients with more residual exocrine gland function might better benefit from RTX. Efficacy of RTX in SS-associated B-cell lymphoma, mainly in low-grade salivary gland lymphomas, remains an open issue.