There have been few changes over the last 50 years in the treatment of Systemic 
lupus erythematosus (SLE), using non-specific anti-inflammatory agents such as: 
nonsteroidal anti-inflammatory drugs along with the immune cell modulating agent 
hydroxychloroquine for mild disease, and broad spectrum immunosuppressants plus 
antiinflammatories such as corticosteroids, azathioprine, cyclophosphamide, or 
mycophenolate during flares or severe disease with organ involvement. In some 
patients, the response is inadequate and side effects appear from mild 
unpleasant up to severe toxicity. Drug metabolism and clearance may be severely 
compromised. Therefore, it is a priority to develop better treatments with fewer 
adverse events that can be used at different stages of disease activity. In 
recent years, a member of the tumor necrosis factor (TNF) family, soluble human 
B Lymphocyte Stimulator protein (BLyS), also referred to as B-cell activating 
factor (BAFF) and TNFSF13B has been studied extensively. This protein is 
synthesized by myeloid cell lines, specifically interacts with B lymphocytes and 
increases their life-span. BlyS plays a key role in the selection, maturation 
and survival of B cells and it has a significant role in the pathogenesis of 
SLE. In this review, we analyzed the role of BLyS as a diagnostic/prognostic 
marker and/or therapeutic target for lupus patients, and the different clinical 
studies published using belimumab.