Nervous system involvement in systemic lupus erythematosus (SLE) is typically diagnosed on the basis of clinical psychiatric and/or neurologic syndromes (NPSLE). Neuropsychological tests can be used to assess nervous system integrity even in the absence of major NP syndromes. Their application has uncovered significant cognitive dysfunction, ranging from mild to severe, in a sizeable proportion of SLE patients irrespective of clinical NP status. Cognitive dysfunction has now been accepted as a bona fide manifestation of NPSLE. The heterogeneity of clinical NPSLE manifestations is paralleled by the diversity of cognitive deficits reported in different studies and within different patients. The success of attempts to explain these deficits on the basis of potential pathogenetic mechanisms, such as antibrain antibodies and proinflammatory cytokines, has been uneven. To date, the most robust findings have emerged in relation to antiphospholipid antibodies, which carry with them important therapeutic implications.