There has been unprecedented growth in new therapeutic approaches for the treatment of systemic lupus erythematosus (SLE). These approaches include re-evaluation of the doses and duration of therapy with traditional agents, including intravenous cyclophosphamide and azathioprine. Drugs that were developed for other uses are being applied to specific SLE manifestations, and have spurred larger scale trials for overall disease activity. In addition, several new agents show promise in clinical trials; many have safer toxicity profiles than do traditional therapies. Some of these agents have multiple immunomodulatory effects, whereas others interfere with a specific immunologic process in one of the pathogenetic pathways of SLE activity.