Treatment of patients with systemic lupus erythematosus (SLE) is still a challenge for many physicians and often associated with a range of adverse side effects. Based on the evidence of the central role of B cells in SLE pathogenesis, several new drugs have been developed. Inhibition of BAFF/APRIL system has appeared as one of the key factors in modulating B-cell response in patients with SLE. In 2011, belimumab was approved by the European and American regulatory agencies for the treatment of SLE patients. Four years later, consistent clinical experience has been accumulated. This article aims to review the mechanisms behind this system and the evidence provided by up-to-date trials on the safety, efficacy and effectiveness of belimumab in SLE patients.