Acute tubular necrosis (ATN) due to bisphosphonates has been reported with Zoledronic acid but the time to recovery (if any) has been usually less than 4 months. Possible recovery time from ATN of any cause is usually less than 6 months. In this paper, we present the case of a 59-year-old Caucasian female with metastatic breast cancer who had received 16 monthly injections of Zoledronic acid for treatment of tumor induced hypercalcemia and developed several episodes of mild acute kidney injury which resolved by withholding treatment. Unfortunately, after the sixteenth injection, the patient experienced severe acute kidney injury, with a peak serum creatinine of 8.0 mg/dL. Although urinalysis showed muddy brown casts, because of atypical recovery time and presence of eosinophiluria and subnephrotic range proteinuria, a kidney biopsy was performed. Diagnosis of typical acute tubular necrosis was confirmed without any other concomitant findings. The course was remarkable for an unusually slow recovery of renal function over 15 months without need for renal replacement therapy until the patient expired from her metastatic cancer two years later. We reviewed all the published cases of acute kidney injury due to Zoledronic acid and suggest recommendations for clinicians and researchers.