Treatment for systemic lupus erythematosus (SLE) has traditionally been restricted to broad-based immunosuppression, with glucocorticoids being central to care. Recent insights into lupus pathogenesis promise new, selective therapies with more favorable side effect profiles. The best example of this is belimumab, which targets the B cell cytokine BLyS and has now received Food and Drug Administration (FDA) approval for its use in SLE. Strategies targeting other cytokines, such as interleukin 6 (IL-6) and interferon (IFN)-α, are also on the horizon. Blockade of costimulatory interactions between immune cells offers another opportunity for therapeutic intervention, as do small molecule inhibitors that interfere with cell signaling pathways. We review here the current strategies for SLE treatment, with particular focus on therapies now in active pharmaceutical development. We will also discuss new understandings in lupus pathogenesis that may lead to future advances in therapy.