Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by multisystemic involvement and diverse manifestations. Neuropsychiatric systemic lupus erythematosus (NPSLE) is a complex neurological disorder characterized by neuropsychological dysfunction. NPSLE is associated with increased morbidity and mortality. In 1999, the American College of Rheumatology developed 19 discrete neuropsychiatric syndromes that comprised NPSLE. Nervous system disease in systemic lupus erythematosus is manifested by a wide variety of clinical manifestations. The pathogenesis of NPSLE is due to autoantibodies, neuronal and non neuronal antigens and the generation of proinflammatory cytokines and mediators. Anatomopathological lesions are attributed to in situ thrombosis, edema, hemorrhage, vasculitis, atherosclerosis or atheroembolism. The diagnosis of NPSLE remains largely one of exclusion and is approached by clinical evaluation, and supported when necessary by autoantibody profiles, diagnostic imaging, electrophysiologic studies and objective assessment of cognitive performance. Brain MRI abnormalities in NPSLE might show small punctate focal lesions in white matter being the most common MRI finding, followed by cortical atrophy, ventricular dilation, cerebral edema, diffuse white matter abnormalities, focal atrophy, cerebral infarction, acute leukoencephalopathy and intracranial hemorrhage. The treatment is based on the use of symptomatic therapies, immunosuppressives and non-pharmacologic interventions. This review paper was designed to understand the pathophysiology for better management of NPSLE.