Benlysta (belimumab) is a fully human recombinant monoclonal IgG antibody that neutralizes soluble B-lymphocyte stimulator and inhibits its biologic activity. Benlysta was recently approved by the US Food and Drug Administration to treat systemic lupus erythematosus (SLE). The current review discusses the data from the belimumab clinical trials and the role of this new medication in the treatment of SLE. We propose that Benlysta should be used in antinuclear antibody–positive patients with active disease in whom the goal of therapy is to decrease SLE activity, reduce flares, and help lower background medications. With this being the first drug approved for treatment of SLE in 50 years, patients have more treatment options, while researchers have a greater understanding of SLE and clinical trial design in such a heterogeneous disease.