The term ‘legacy effect’—a memory of a treatment which produces benefits long after the cessation of the intervention—was adopted for the first time to describe the benefits of early and strict control of diabetes on cardiovascular complications. The search for a similar effect for early treatment of immune-mediated renal diseases, interrupting some self-amplification loops of the pathogenetical immunological mechanisms and leaving a permanent memory, is fascinating. Some recent reports suggest a long-term beneficial or legacy effect of early treatment of IgA nephropathy after a randomized controlled trial (RCT) using mycophenolate mofetil, methylprednisolone pulses or steroid/immunosuppressive multiple therapy, or prolonged steroid doses associated with tonsillectomy. Long-lasting effects of treatments are more likely to be achieved in early stages of IgA nephropathy, when mesangial proliferative or endocapillary hypercellular lesions are pre-eminent over sclerosis, and when proteinuria is not massive, above all in young patients. The long-term results considered are relevant, but have the counterpart of the risk of drug toxicity or side effects, which are particularly undesired in patients with a mild disease. Hence, there is interest for drugs targeting the intestinal mucosal immunity with a little systemic effect, aimed at interrupting the initial pathogenetical mechanism. The possibility of modulating anti-inflammatory regulatory T cells by modifying inducible enzymes is another fascinating field of future research.