Bisphosphonates are commonly used for the treatment of osteoporosis, Paget's disease, multiple myeloma and hypercalcemia. Collapsing focal segmental glomerulosclerosis (FSGS) is known to occur uncommonly with exposure to bisphosphonates, specifically pamidronate and alendronate; it has rarely and equivocally been reported with zoledronate therapy. We describe the case of a 36-year-old African American female with metastatic breast cancer who presented with nephrotic-range proteinuria and acute kidney injury within 2 weeks of exposure to a single dose of zoledronate. The patient had a partial recovery of her renal function and showed improved proteinuria to a subnephrotic level after discontinuing zoledronate. In contrast to 2 prior reports of zoledronate-induced collapsing FSGS, the causative role of the exposure described here is certain. Our case necessitates the addition of zoledronate to the list of known causes of collapsing FSGS. Furthermore, it highlights the importance of periodically monitoring renal function and urine protein excretion with the use of zoledronate, which allows prompt diagnosis and withdrawal of the drug to increase the probability of renal recovery.