Acute renal failure (ARF) is a rare but severe complication of active idiopathic nephrotic syndrome (INS) in children. It may be due to several causes with different outcomes. Both the clinical picture of the patient as well as laboratory, imaging and histopathological findings may help in the diagnosis. We present a case of drug-induced acute interstitial nephritis (AIN), complicated with ARF, in a 2(1/2) -year-old girl with active INS. The child was referred to the Hippokration General Hospital, Thessaloniki, Greece hospital with steroid-resistant NS; renal biopsy was performed, which did not show any remarkable findings and cyclosporine was administered in addition to steroid therapy. The first day after biopsy, the child developed gross hematuria and abdominal pain and an antibiotic was added to her treatment. In the following days, fever, vomiting, hypertension and ARF occurred. Ultrasound study revealed enlarged kidneys with increased echogenity and loss of corticomedullary differentiation. The antibiotic and cyclosporine were stopped and the child was managed with furosemide, nifedipine and steroids. A second renal biopsy was performed, which confirmed the diagnosis of acute interstitial nephritis. The child did not require dialysis therapy. Her urine output improved gradually and the serum creatinine normalized one month after the initial episode. Our case re-emphasizes the need for investigation of factors precipitating ARF in children with idiopathic NS.