Background: Alendronate is considered a safe drug with respect to kidney function when used per manufacturer recommendations. Objective: To describe reported cases of nephrotoxicity associated with alendronate. Methods: Pubmed search of English literature up to January 14, 2022. Search terms include alendronate, bisphosphonates, proteinuria, renal failure, adverse effects. Pertinent case reports, reviews, and guidelines of professional organizations are included. Results: Review of literature revealed 7 patients who developed nephrotoxicity likely due to alendronate therapy for osteoporosis. In 5 patients, kidney function was normal before starting alendronate. Five patients presented with nephrotic syndrome and had focal segmental glomerulosclerosis (FSGS) on renal biopsy. Collapsing FSGS was specifically demonstrated in 2 patients. Nephrotoxicity was diagnosed as early as 2 weeks and up to 3 years after starting alendronate. No clear predisposing factors or patient demographic characteristics could be outlined in association with this adverse effect. In addition to discontinuation of alendronate, treatment consisted of glucocorticoids followed by angiotensin-converting enzyme inhibitors and diuretics. In 4 of the 7 patients, renal function did not return to normal and 3 subjects required hemodialysis. Conclusions: Physicians should be aware that alendronate may be uncommonly associated with nephrotoxicity. Checking protein in urine 2 weeks after starting alendronate and periodically thereafter may help early diagnosis of this serious adverse effect.