Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease characterised by dysfunction and inflammatory lymphocytic infiltration of exocrine glands, namely the salivary and lacrimal glands. pSS patients often suffer from sicca (dry mouth) complaints, including dental caries, and difficulties in eating, sleeping and speaking. A large body of literature points to a central role for salivary gland (SG) epithelial cells in the development of this pathology. Here we summarise recent studies concerning the role of SG epithelial cells in pSS, which strongly indicate their intrinsic activation and early involvement during the disease process. Based on that, we propose possible future interventions targeting SG epithelial cells, to treat SG dysfunction pSS.