Since the current standards for drug approval were established nearly half a century ago, no drug has been approved for the treatment of systemic lupus erythematosus (SLE). Despite this sobering history, interest in drug development for SLE has heightened in the past few years. This enthusiasm has been fueled in large part by the success of biologic therapy for rheumatoid arthritis and other autoimmune diseases. Unfortunately, despite considerable clinical trial activity, this interest has not yet translated into the discovery of an effective treatment for SLE. This article provides an analysis of the major clinical trials in SLE, and offers an interpretation of the results that could illuminate the path forward.