Immunosenescence is defined as all the changes occurring in the immune system in the aged. Recent studies suggest that in older patients the immune system undergoes a functional remodelling. Two contrasting phenomena coexist in immunosenescence: the decreasing of immune response and the autoantibody production. Possible consequences are an increase of autoimmune phenomenon, neoplasia incidence, and predisposition to infections. The study of autoimmune manifestations in the elderly population should be considered as a priority for future medical research because of the increase in life expectancy, especially in developed countries. This review analyzes the clinical expression of systemic autoimmune diseases in older patients.