Data regarding the efficacy and safety of infliximab for the treatment of systemic lupus erythematosus come primarily from case reports and small open-label studies. These data suggest a potential benefit for infliximab in patients with active systemic lupus erythematosus along with an adequate safety profile when used in the short term. However, more robust evidence from well-conducted, randomized, controlled trials is needed. Atacicept has demonstrated adequate pharmacodynamic properties in early Phase studies. This molecule reduces the level of immunoglobulins and B cells. However, clinical data regarding its efficacy and safety profile are still not available. The same applies to LY2127399. In this journey for the search of new treatment options for systemic lupus erythematosus, we need to set some priorities and recognize potential pitfalls; that is, drugs need to be tested in patients with severe lupus manifestations; their efficacy and safety profile determined, preferably with adequate long-term data; finally, how these compounds will reach more than a limited number of patients will need to be considered as well.