Sjögren's syndrome (SS) is a systemic autoimmune disease that mainly affects the exocrine glands and usually presents as persistent dryness of the mouth and eyes. SS primarily affects white perimenopausal women, with an incidence of 4-5 cases per 100 000. Recent studies have analysed new therapeutic approaches, focusing mainly on the use of biological agents. B-cell targeted therapies seem to be the most promising agents in primary SS, especially rituximab, which has been used in more than 50 reported cases. Other promising B-cell targeted therapies include epratuzumab and belimumab, while T-cell targeted agents (efalizumab, abatacept, alefacept) should currently be considered as possible future options. In the near future, biological agents will play key roles in the treatment of severe involvement, broadening the therapeutic options in primary SS and offering a more optimistic point of view of the treatment of this disease, which, at present, is often considered to lack adequate specific therapy. However, the possible risks and benefits of using these agents should be carefully balanced, and a reasonable assessment of the risk of serious adverse events versus the benefits of treatment should be made. The use of biological agents targeting molecules and receptors involved in the aetiopathogenesis of primary SS opens a new era in the therapeutic management of patients with primary SS.