Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple lesions that cause inflammation and the production of autoantibodies. Lupus nephritis (LN) and neuropsychiatric SLE (NPSLE) are common organ-threatening manifestations of SLE and result in significant morbidity and mortality. In the last 30 years, steroids and immunosuppressive drugs have improved the prognosis of patients with SLE, and today the 5-year survival rate exceeds 90%. However, the treatment of SLE still largely depends on these medications and sometimes results in death due to complications. In recent years, biologic agents and low-molecular-weight compounds have emerged that are expected to be effective against refractory LN and NPSLE. For the diagnosis of SLE, the classification revised in 1997 proposed by the American College of Rheumatology and the classification standards of the Systemic Lupus International Collaborating Clinics 2012 classification criteria have been used, but they are not necessarily useful for early diagnosis. New biomarkers are needed for the early diagnosis of SLE. In this article, we summarize the unmet needs of diagnosis and treatment with SLE, especially those with LN and NPSLE, with data from our own experiences.