Belimumab (Benlysta ®) is a fully humanized monoclonal antibody that inhibits B lymphocyte stimulator (BLyS, also known as B cell-activating factor of the tumor necrosis factor family) and was approved by the US Food and Drug Administration (FDA) and the European Medicines Evaluation Agency for the treatment of autoantibody-positive systemic lupus erythematosus (SLE) in adults with moderate disease activity. Belimumab was recently FDA approved for use in children with SLE between 5 and 17 years of age. This review discusses the key findings of the belimumab phase III trials in adult SLE (via intravenous and subcutaneous administrations), phase II trial in pediatric SLE (intravenous administration), and post hoc analyses. It also evaluates the current clinical trials of belimumab in specific SLE disease states and highlights the safety profile of belimumab. It discusses the clinical post-marketing use of belimumab in adults and children with SLE and concludes with our recommendations for the use of belimumab to treat pediatric SLE, including a look to the future with increased real-world use in children with SLE.