Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disease. Neuropsychiatric manifestations of SLE (NPSLE) are associated with increased morbidity and mortality. According to the American College of Rheumatology (ACR) classification, NPSLE consists of two broad categories: central and peripheral nervous system syndromes, which cover a wide range of clinical presentations such as stroke, seizures, and psychosis. The aim of targeted treatment for SLE is to reduce damage accrual; damage can be reduced by controlling the disease activity, minimizing the use of corticosteroids, and optimizing the management of comorbidities like cardiovascular risk factors. In patients with life- or organ-threatening manifestations of SLE, the combined use of high-dose corticosteroid and immunosuppressants, such as cyclophosphamide pulse and mycophenolate mofetil, is necessary. If patients do not respond to conventional treatment, biological agents, including anti-BAFF, anti-CD20, anti-CD22, and CTLA4-Ig, are additional available therapies. A more effective and less toxic approach to SLE treatment remains to be found.