OBJECTIVES: Rituximab is monoclonal antibody that targets B-cells, acting as a powerful immunosuppressant agent. This study evaluated the efficacy and safety of rituximab for systemic lupus erythematosus (LES) treatment, an off-label use. METHODS: Medline (via Pubmed), The Cochrane Library (via Bireme), Lilacs and the Centre for Reviews Dissemination (CRD) were searched randomized controlled trials (RCT) and for systematic reviews (SR) of clinical trials and/or observational studies comparing rituximab with placebo in the pharmacotherapy of adults with active systemic lupus erythematosus. The quality of evidence and strength of recommendation were assessed using the GRADE system.  RESULTS: Two SR with meta-analysis and three RCT were included, whose quality ranged from very low to moderate. One systematic review that included 19 observational studies and 2 RCT showed favorable results for rituximab when compared to placebo or in addition to glucocorticoid with respect to SLEDAI score and reduction in glucocorticoid dose. For BILAG score and renal function the results were not statistically significant. The other SR included three RCT and did not show favorable results for rituximab in addition to glucocorticoid+antimalaric+imunosupressant. One RCT showed a temporal benefit with rituximab use – patients exposed to it showed reduction in disease activity index four months earlier than patients who did not use it in addition to cyclophosphamide. The other two RCT showed good results for rituximab in addition to glucocorticoids+immunospresasant in serological outcomes. In all SRs and RCTs rituximab presented a satisfactory safety profile. CONCLUSIONS: Rituximab results for systemic lupus erythematosus treatment are modest and inconclusive. This is confirmed by the fact that the producer itself has not solicited rituximab licensing for LES in FDA or EMA. With data published until now, off-label use should be restricted and discouraged. LES patients remain awaiting for an effective new technology.