Nephrotic syndrome (NS) secondary to drug-induced acute interstitial nephritis (AIN) is well described in adult but is very rare in children. We report an unusual case of AIN mimicking prototypical childhood minimal change NS. A 2-year-old girl on long-standing amoxicillin therapy for vesicoureteral reflux presented with the acute onset of generalized edema, proteinuria, hypoalbuminemia, hypercholesterolemia, and an inactive urinary sediment. She was placed on empiric steroid therapy for presumed minimal change NS. When she did not respond to steroids, a renal biopsy was performed and revealed AIN. Her NS resolved completely with cessation of her amoxicillin therapy and concomitant tapering of her steroids. This patient demonstrates that the association of AIN with NS should be carefully considered in children on antimicrobials who develop NS, even in the absence of the classic clinical features of AIN. In addition to the usual work-up and care of a child with NS, in these patients consideration may also need to be given to withdrawal of the potential precipitating agent.