Belimumab is a fully human recombinant IgG1λ monoclonal antibody that inhibits the binding of soluble B lymphocyte stimulator to B cells and hence prevents the survival and differentiation of selected B-cell subsets. It is available in the US, the EU and Canada for the treatment of adult patients with active, autoantibody-positive systemic lupus erythematosus (SLE) with a high degree of disease activity despite receiving standard therapy. At 52 weeks, a significantly greater proportion of belimumab 10 mg/kg than placebo recipients experienced a response as assessed by the SLE Responder Index (primary endpoint) in the randomized, double-blind, multinational, phase III BLISS-52 and BLISS-76 trials in patients with active seropositive SLE receiving standard therapy. A significantly greater proportion of belimumab than placebo recipients achieved a ≥4 point reduction in the SELENA-SLEDAI score at week 52 in both BLISS trials. However, the SLE Responder Index response rate was not significantly different between belimumab and placebo at 76 weeks in BLISS-76. Belimumab was generally well tolerated in the BLISS trials. During the double-blind periods of these trials and the phase II trial, twice as many deaths were reported with belimumab than placebo (six vs three). There were no meaningful differences between the incidence of serious infections and malignancies with belimumab or placebo.