Purpose of review Lupus nephritis (LN) is a serious manifestation of systemic lupus erythematosus and is characterized by proteinuria and renal failure. Proteinuria is a marker of poor prognosis and is attributed to podocyte loss and dysfunction. It is often debated whether these cells are innocent bystanders or active participants in the pathogenesis of glomerulonephritis. Recent findings Podocytes share many elements of the innate and adaptive immune system. Specifically, they produce and express complement components and receptors which when dysregulated appear to contribute to podocyte damage and LN. In parallel, podocytes express major histocompatibility complex and co-stimulatory molecules which may be involved in local immune events. Podocyte-specific cytotoxic cells and possibly other immune cells contribute to glomerular damage. Autoantibodies present in lupus sera enter podocytes to upregulate calcium/calmodulin kinase which in turn compromises their structure and function. Summary More recent studies point to the restoration of podocyte function using cell targeted approaches to prevent and treat LN. These strategies along with podocyte involvement in the pathogenesis of LN will be addressed in this review.