Autoimmunity is a leading cause of chronic kidney disease and loss of native and transplanted kidneys. Conventional immunosuppressive therapies can be effective but are non-specific, noncurative, and risk serious side effects such as life-threatening infection and cancer. Novel therapies and targeted interventions are urgently needed. In this brief review we explore diverse strategies currently in development and under consideration to interrupt underlying disease mechanisms in immune-mediated renal injury. Because autoantibodies are prominent in diagnosis and pathogenesis in multiple human glomerulopathies, we highlight several promising therapies that interfere with functions of early mediators (IgG and complement) of the effector arm and with an epicenter (the germinal center) for induction of humoral immunity.