Systemic lupus erythematosus is a complex autoimmune disorder affecting multiple organ systems. Glomerulonephritis leading to severe proteinuria, chronic renal failure and end-stage renal disease remains one of the most severe complications of systemic lupus erythematosus and is associated with significant morbidity and mortality. Conventional lupus nephritis (LN) treatment based on cyclophosphamide, steroids and, recently, mycophenolatemofetil has improved the outcome of the disease over the last 50 years, although failure to achieve remission or treatment resistance has been reported in 18-57% of patients. Chronic complications such as long-term toxicity dampen their ability to maintain disease remission. There is a need to develop more specific pharmacological agents for patients to provide choices that are equally effective, less toxic and have fewer complications. During the last 10 years, experimental studies based on different pathogenesis pathways of LN have provided an enormous amount of knowledge and have offered the possibility to target the disease with selective approaches. In this article, we summarize the new experimental strategies that have recently been utilized to target LN, focusing on mechanisms of action.