Introduction: Major trials hoping to obtain optimal disease control in systemic lupus erythematosus (SLE) are ongoing. Given its complex aetiology and pathogenesis, it is not surprising that multiple therapeutic targets have emerged and that none are uniformly successful. Areas covered: In this review, we highlight the recent, more significant studies focusing on the use of biologic therapies. There has been great emphasis on the role of B cells in SLE and many uncontrolled studies have encouraged the use of rituximab (an anti-CD20 monoclonal). Disappointingly, two major trials, EXPLORER and LUNAR did not confirm its utility, although doubts have been expressed on their trial design, and other trials using this drug are commencing. In contrast, belimumab, which blocks a B-cell activating factor, did meet its end points in two major randomised controlled clinical trials and has been approved for use in SLE by both the FDA and the European Medicines Agency. Encouraging, albeit preliminary, results with epratuzumab (which blocks CD22) have also been reported. Expert opinion: In addition to targeting B cells, other approaches including biologics, which modulate T-cell function and block interleukin-6 and interferon-alpha, have been explored. Finally, we review the recent developments in the use of conventional drugs, such as cyclophosphamide and mycophenolate.