The March 2011 approval of belimumab (Benlysta) by the US Food and Drug Administration has left rheumatologists in a bit of a quandary regarding its use. It is officially intended for adult patients with autoantibody-positive systemic lupus erythematosus whose disease remains active despite receipt of standard-of-care therapy. The approved indication is broad and leaves interpretation to individual rheumatologists. Analyses of the phase 2 and 3 clinical trials of belimumab help answer some of the commonly asked questions, such as the following: 1) Who is the appropriate patient for belimumab? 2) How does one measure response? 3) When should results be expected in a patient newly treated with belimumab? 4) When should belimumab be discontinued?