Systemic lupus erythematosus (SLE) is a difficult disease to study, having a variable disease course characterized by exacerbations and remissions. A variety of biologic agents are under investigation as potential treatments for SLE. These products are designed to specifically interfere with the following immuno-logic processes: T cell activation/T cell—B cell collaboration, production of anti-double-stranded DMA antibodies, deposition of anti-double-stranded DMA antibody complexes, complement activation, and immune complex deposition and cytokine activation and modulation. More aggressive interventions include gene therapy and stem cell transplantation. Immunomodulatory agents recently examined in patients with SLE include: thalidomide, AS101, 2'chlordeoxyadenosine, mycophenolate mofetil, and bindarit. Additional innovative pharmaceutical treatments include the mild androgen dehydroepiandrosterone, selective estrogen receptor modulators, and the prolactin inhibitor, bromocriptine. A variety of these biologic and pharmaceutical agents offer promise as potential therapies. Active participation in clinical trial efforts to develop international consensus regarding trial methodology and outcome measures are crucial to the development of these innovative therapies.