Juvenile polyarteritis nodosa, a rare systemic vasculitis, may present with a wide variety of clinical manifestations. Neurologic involvement has been reported in as high as 50% to 70% of patients; however, the incidence of cranial nerve palsies is extremely uncommon. We report here the case of a 20-month-old girl with juvenile polyarteritis nodosa who developed cranial nerve III palsy, demonstrated both clinically and radiographically on MRI despite aggressive management with immunosuppressants. Neurologic manifestations resolved with treatment including corticosteroids and cyclophosphamide; however, persistent fevers, rash, and headaches interfered with attempts at a corticosteroid taper. Subsequent therapy with a combination of mycophenolate mofetil and infliximab proved highly efficacious in inducing disease remission and eventual discontinuation of corticosteroids. Knowledge about the management of refractory juvenile polyarteritis nodosa is limited. Here we report a rare case of cranial nerve involvement, as demonstrated on MRI, and successful management with a regimen of mycophenolate mofetil and infliximab.