Sjögren's syndrome (SS) is a complex autoimmune disorder, characterised by mononuclear cell infiltration of exocrine glands, principally the lacrimal and salivary glands. Both cellular, in the form of autoreactive immune cells, and humoral factors, such as autoantibodies, contribute to the expression of the disease. SS can also occur as a systemic disease affecting several organs, and approximately 5% of the patients develop malignant lymphoproliferation. Today SS is considered uncurable. The treatment available is only palliative, and the treatment goals are to manage symptoms and prevent or limit tissue damage. This may involve both local and systemic measures. However, the existing systemic treatment of chronic inflammatory autoimmune diseases has several limitations and unwanted side effects. In recent years the possibility to treat diseases with gene therapy has gained interest and has become a subject of investigation. Given the multitude of factors contributing to the pathogenesis of SS, gene therapy is a major challenge, but may elicit great benefits if successful. Keeping this in mind, the possibility for gene therapeutics in SS in general and potential targets for gene therapy are discussed.