Abstract The etiology of autoimmune disease is multifactorial, including genetic, environmental, hormonal, and immunological factors. Nevertheless, the onset of autoimmune disorders remains enigmatic. Physical and psychological stresses have been suggested in the development of autoimmune disease, since numerous animal and human studies demonstrated the effect of stressors on immune function. Moreover, many retrospective studies had found that a high proportion (up to 80%) of patients reported uncommon emotional stress before disease onset. This, however, is not surprising as the disease itself causes significant stress in the patient. Recent reviews discuss the possible role of psychological stress, and of the major stress-related hormones, in the pathogenesis of autoimmune disease and presume that the stress-triggered neuroendocrine hormones lead to immune dysregulation, which ultimately results in autoimmune disease by altering or amplifying cytokine production. However, there is no evidence based research to support this concept. Nonetheless, stress reactions should be discussed with autoimmune patients. Applied implications are discussed, concentrating on the need for multidisciplinary care interventions that target patients' disease symptoms and help them cope with their illness.