Juvenile Systemic Lupus Erythematosus (jSLE) is a chronic and multisystemmic autoimmune disease, which appears before 16 years old with an incidence of 10 to 20 cases per 100,000 children. The clinical spectrum of jSLE can be quite variable. The most common symptoms are constitutional, followed by the cutaneous, musculoskeletal, renal, and neuropsychiatric involvement. Neuropsychiatric involvement in jSLE has a prevalence ranging from 20 to 50.9% and results in significant morbidity and mortality. The most common clinical manifestations of juvenile neuropsychiatric SLE (NPSLE) are headache, cognitive dysfunction, mood disturbances and seizures. The pathophysiology of juvenile NPSLE is not yet fully known, but immunological and inflammatory factors, such as autoantibodies, cytokines and prothrombotic states are widely described. The role of autoantibodies in the onset of specific clinical manifestations has also been recognized. Juvenile NPSLE manifestations are often difficult to diagnose. In addition to semiological aspects, the study and validation of neuropsychological testing and neurocognitive assessment for the juvenile SLE population are essential. The role of advanced imaging techniques should be explored. The treatment of juvenile NPSLE must be individualized according to the type and severity of clinical manifestations, relying on symptomatic therapy, anticoagulants or steroids. New therapeutic approaches, including biotherapies need controlled randomized trials for further validation. This article aims to review the pathogenesis, clinical manifestations, diagnosis and treatment of juvenile NPSLE.