BACKGROUND: There is still unmet medical need in the therapy of severe organ manifestations of patients with systemic lupus erythematosus (SLE). Therapeutic agents targeting pro-inflammatory cytokines may be an interesting option. OBJECTIVE: To review available data on the efficacy and safety of tumour necrosis factor (TNF) blockade in SLE. METHODS: A review of the literature was conducted. RESULTS/CONCLUSIONS: Open-label experience suggests that TNF blockade is effective in SLE patients with arthritis, nephritis and skin disease. In particular, nephritis may remain in long-term remission after just four infusions of infliximab administered. Despite the induction of lupus-specific autoantibodies, short-term therapy with infliximab in combination with azathioprine appears feasible and relatively safe. The data call for controlled clinical trials, at least one of which has been initiated.