Acute Interstitial Nephritis (AIN) is a significant cause of acute kidney injury (AKI), often associated with polypharmacy, especially in older adults. It accounts for 15–20% of AKI cases, with drug-induced AIN (DI-AIN) being the predominant form. DI-AIN is a dose-independent type IV hypersensitivity reaction involving T lymphocytes, commonly triggered by antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs), and proton pump inhibitors (PPIs). Diagnosis is typically confirmed through renal biopsy, revealing interstitial infiltrates primarily composed of lymphocytes and monocytes. Clinical presentation varies from asymptomatic serum creatinine elevation to the classic triad of fever, rash, and eosinophilia. Prompt discontinuation of the offending drug and early corticosteroid therapy are essential for effective management and to prevent chronic kidney disease progression.