Primary Sjögren's syndrome is an autoimmune disease characterized by lymphocytic infiltration of glandular tissues leading to sicca symptoms, namely, dry eyes and dry mouth. In the majority of cases, the disease course is benign, albeit with considerable patient discomfort. Some patients, however, have systemic symptoms with arthritis, cutaneous vasculitis, low complement levels, and cryoglobulinemia. A small but not insignificant percentage of those patients evolve to B cell lymphoma. The increased expression of B cell survival factors, such as B cell activating factor, may promote the perpetuation of a B cell clone and precede the lymphoproliferative disease. Rituximab, a chimeric monoclonal antibody to CD20, leads to B cell depletion and may have a role in Sjögren systemic manifestations as well as in preventing and treating Sjögren-associated lymphoma.