Nephrotic syndrome (NS) associated with renal artery stenosis is not widely recognized or investigated as a cause of the NS. The mechanisms are incompletely understood, but have largely focused on hemodynamic factors resulting in hyperfiltration injury-induced focal and segmental glomerulosclerosis (FSGS) in the nonstenosed kidney with sparing of the stenotic kidney protected from hemodynamic stress. However, separation of hemodynamic from circulating factors (such as angiotensin II) as the cause of the nephrosis remains difficult. We report a patient presenting with NS who was incidentally discovered to have high-grade bilateral renal artery stenosis from fibromuscular dysplasia. Kidney biopsy revealed FSGS. Proteinuria in our patient did not initially respond to angiotensin-converting enzyme inhibition (ACEI) and correction of stenoses with angioplasties. There was prompt response to steroid treatment. A brief relapse several months later (without associated hypertension) responded to ACEI alone. This is the first reported case of an association between fibromuscular dysplasia and steroid-responsive nephrotic syndrome due to FSGS. This may shed insight into the nature of podocyte injury in patients with high angiotensin states and suggest a possible role for activated renin-angiotensin-aldosterone system (RAAS) triggering an immune-mediated injury, rather than hemodynamic insult. Furthermore the lack of initial response to angioplasty and ACEI suggests that RAAS-activated injury may in some cases require more aggressive immune modulatory therapy with steroids over and above angiotensin inhibition alone. This case also highlights the importance of being aware of possible occult renovascular disease contributing to idiopathic NS with FSGS even when hypertension is only modest.