BACKGROUND Sjögren's syndrome is an autoimmune disease, and its important feature is the lymphocyte infiltration of exocrine glands, including lacrimal glands. It contributes to defects of their activity and causes that one of the main manifestation of Sjögren's syndrome is dry eye. Unfortunately, the discrimination between dry eye related and non-related to Sjögren's syndrome is difficult at the initial stages of diseases. In addition, the available agents for the treatment of Sjögren's syndrome-related dry eye have limited efficacy. OBJECTIVE The purpose of this study was to describe and emphasize differences between Sjögren's Syndrome-related dry eye and non-Sjögren's Syndrome-related dry eye together with the determination of novel therapeutic options for Sjögren's Syndrome-related dry eye. METHODS A review of the relevant papers describing characteristics of Sjögren's Syndrome-related dry eye and its therapy was conducted. This article is based on both pre-clinical and clinical evidences. RESULTS On the basis of our analysis, we indicated differences between Sjögren's Syndrome-related dry eye and non-Sjögren's Syndrome-related dry eye. Moreover, there are some novel markers that could be used in the diagnosis of Sjögren's Syndrome-related dry eye. In addition, expect artificial tear, other agents e.g. hydroxychloroquine can be effective in therapy of disease. CONCLUSIONS Sjögren's Syndrome-related dry eye is a disorder, whose diagnosis may be difficult and mistaken for non-Sjögren's Syndrome-related dry eye. However, Sjögren's Syndrome-related dry eye has some specific features. In addition, the development of newer and safer therapeutic agents for Sjögren's syndrome-related dry eye is needed, and therefore further clinical, randomized studies are necessary.