Lupus nephritis (LN) is one of the major complications of Systemic Lupus Erythematosus (SLE) and its treatment remains a challenge. Although the classical and widely used immunosuppressive agents have accounted for a significant improvement in the survival and decreased the progression to end-stage renal failure they lack selectivity for the underlying immune dysregulation. In addition the toxicity related to their use and the relapses after treatment are of major concern not least because of the adverse effect on the prognosis of the patients with SLE who have kidney involvement. The development of more specific pharmacological agents for patients with SLE is still a major research goal. Ideally these agents should provide a better long-term prognosis for SLE patients and be less toxic. In this review we summarise the mechanism of action and the results obtained with a variety of drugs that have recently been utilized in the treatment of patients with lupus especially those with nephritis. We discuss the clinical usefulness of B- -cell depletion principally anti-CD20 antibodies blockage of co-stimulatory pathways (anti-CD40 ligand antibody CTLA4Ig) the induction of immune tolerance (LJP 394 peptide specific vaccination) and therapy targeting cytokines (anti-IL10 antibody BLyS blockage) and the complement system (anti-C5 antibody). Immunoablative doses of Cyclophosphamide (CyC) with or without Haematopoietic Stem Cell Transplantation (HSCT) and the possibilities of gene therapy are also reviewed. The use of intravenous immunoglobulin (IVIg) and plasmapheresis are not discussed because these treatments have been used in clinical practice for several years.