(Ludwik Hirszfeld (1884–1954)—Polish physician, microbiologist, immunologist and serologist) Sjögren’s disease is an increasingly well-known autoimmune disease, involving all systems and organs. Its course can range from mild with dominant dryness of mucous membranes or arthralgia to cases with the involvement of the central nervous system and severe cryoglobulinaemic vasculitis. The pathogenesis of the disease is very complex and includes genetic predisposition, the influence of environmental factors and epigenetic modifications to hyperactivity of immune system cells with overproduction of autoantibodies. Currently, its diagnosis is based on the assessment of the immunological variables, presence of dryness of mucous membranes, confirmation of the presence of a characteristic histopathological picture of a biopsy of the minor salivary glands with a focus score gradation. For the establishment of a proper diagnosis, the knowledge of possible exclusionary diseases—similar in some aspects to SjD, such as IgG4-related disease or active HCV infection—is crucial. Treatment of SjD is diverse and is shaped by a clinical and immunological assessment and can range from symptomatic treatment to immunosuppression, cytostatic and biological drugs, and even bone marrow or organ transplantation. The most serious complications of SjD include the development of lymphoma or severe CNS involvement, and lung changes requiring organ transplantation. The advancement of knowledge about the pathogenesis of autoimmune diseases, including SjD and progress of diagnostic methods, including genomic research, has allowed for a better understanding of this complicated disease. However, we have still a lot to learn and discover before we fully comprehend the disease described by Henrik Sjögren over 90 years ago.