About one third of patients with systemic lupus erythematosus (SLE) will present neurological or psychiatric symptoms in the course of the disease. Before attributing neuro-psychiatric illness to SLE, other causes have to be excluded, such as infections and treatment-related toxicity. Some manifestations of neuropsychiatric SLE (NPSLE) reflect active systemic disease, while other arise from chronic damage and may occur during apparent remission. Many clinical pictures are associated with antibodies, such as those targeting phospholipids, N-methyl-D-aspartate-receptor and anti-ribosomal P protein. This review discusses clinical manifestations and pathogenesis of central NPSLE, with a focus on the principal antibodies associated and other diagnostic tools at hand.