Sjogren's syndrome (SS) is a chronic autoimmune disorder affecting mainly middle-aged women. It is characterized by lymphocytic infiltration and destruction of the exocrine glands (mainly the salivary and lacrimal glands), resulting in dry mouth and eyes. Symptoms of SS are chronic and sometimes devastating, compromising the quality of life at a major extent. Despite its autoimmune nature, evidence for the use of immunosuppressive agents, which are the mainstay of therapy of diseases of autoimmune origin, is limited. Keratoconjunctivitis sicca (KCS), the main ocular manifestation of SS, is managed with tear substitutes, as well as local and systemic stimulators of tear secretion and supportive surgical procedures. Management of oral manifestations includes intense oral hygiene, prevention and treatment of oral infections, use of saliva substitutes, and local and systematic stimulation of salivary secretion. Cholinergic agents, such as pilocarpine and cevimeline are the cornerstone of current therapy in SS. Corticosteroids, cyclophoshamide, and nucleoside analogues are reserved for severe extraglandular manifestations of SS. The role of anti-B-cell therapy is a promising option for glandular and extraglandular manifestations of the disease, as well as for the management of SS-associated lymphoma.