Systemic lupus erythematosus (SLE) is a chronic inflammatory disorder that is 
driven by autoantibodies that target multiple organ systems. B-lymphocyte 
stimulator (BLyS) and its receptors on B-cell subsets play an important role in 
autoimmune B-cell development and SLE pathogenesis. Targeted therapy with 
belimumab, the monoclonal antibody against BLyS, has shown clinical benefit in 
two large-scale, multicenter phase III trials leading to US Food and Drug 
Administration approval for patients with serologically positive SLE who have 
active disease despite standard therapy. This review will discuss the challenges 
in lupus drug development and clinical trials, the basics of B-cell pathogenesis 
in SLE, the recent lupus clinical trials of B-cell targeted treatments, and 
other potential targeted therapies under investigation for patients with lupus.