SS is a progressive autoimmune disease characterized by chronic inflammation and lymphocytic infiltration of the exocrine glands that may occur alone (primary SS) or with a comorbid autoimmune condition (secondary SS). Symptomatic therapies to treat dry eyes, dry mouth, or specific extraglandular manifestations are the cornerstone of disease management. Systemic manifestations are most often treated with hydroxychloroquine or, in severe cases, systemic immunomodulators (e.g., azathioprine, methotrexate). Dry eye in SS is treated with eye drops (e.g., Novartis’s Xiidra); dry mouth is treated with artificial saliva or muscarinic receptor agonists. Therapies with disease-modifying potential are in development for SS, targeting key pathways believed to drive pathological processes in the disease. These putative disease-modifying therapies have the potential to transform the management of SS, although SS is an indication in which success has historically proven to be a challenge.