During the last 10 years our increasing understanding of the immunopathogenesis of systemic lupus erythematosus (SLE) has led to the introduction of several new biological therapies. SLE treatment has moved from the use of conventional drugs such as hydroxychloroquine, corticosteroids, and non-specific immunosuppressants to targeting selective components of the immune system in the hope that they can be more effective and reduce undesired side-effects. These new treatments include B-cell-depleting therapies, antibodies and fusion proteins that block interleukins or the cross-talk between B and T cells, and tolerogens. However, although there are great expectations about new agents, double-blind controlled trials demonstrating safety and efficacy are still awaited, and better instruments for evaluating disease activity need to be developed.