The purpose of this review was to explore the probable etiologies of psychiatric problems in patients with SLE. Although instances of psychosis generally are attributed to disease pathophysiology, the precise mechanism for this problem remains speculative. The etiology of non-psychotic psychiatric complaints is even less clear. Overall, it is likely that psychiatric complaints in patients with SLE are attributable to numerous factors including acquired brain dysfunction, organ system dysfunction, iatrogenic effects of corticosteroid treatment, learning history, psychosocial stressors, and current coping strategies. Additional research is needed to explore the bi-directional, synergistic, and dynamic interactions among diverse physiological and psychological variables as they impact an individual's psychiatric status.