Among youth with incident nephrotic syndrome, those with steroid-resistant nephrotic syndrome (SRNS) often have an ominous clinical course. Identifying them at or shortly after diagnosis would potentially prevent substantial morbidity and even mortality. For those with a specific monogenic form, targeted therapy might be possible, as is the case presently for CoQ10 insufficiency cases. Further, dissecting specific causes and pathways that lead to SRNS may lead to other targeted, potentially highly effective treatments.