Sjögren’s syndrome (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, and/or specific extraglandular manifestations (commonly arthralgia and fatigue) are the cornerstone of disease management. Systemic manifestations are most often treated with hydroxychloroquine or, in severe cases, systemic immunomodulators (e.g., azathioprine, methotrexate). Therapies with disease-modifying potential (e.g., Novartis’s iscalimab and ianalumab) 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 such success has been a challenge to date.