Cisplatin, a widely used and effective cancer chemotherapeutic agent, is known for its nephrotoxicity, which can lead to acute kidney injury (AKI) in up to 30% of patients. This review discusses recent advances in understanding the cellular mechanisms underlying cisplatin-induced renal cell death and the role of inflammation in exacerbating kidney injury. Cisplatin accumulation in the kidney is facilitated by transporters such as Ctrl and OCT2, leading to DNA and mitochondrial damage. Apoptotic pathways, including intrinsic and extrinsic pathways, are activated, contributing to renal epithelial cell death. Inflammation, mediated by cytokines like TNF-α and toll-like receptors (TLRs), plays a crucial role in amplifying kidney injury. The review also explores preventive strategies, including volume expansion, amifostine, and targeting cisplatin uptake and inflammation, highlighting the need for careful evaluation of these strategies to ensure they do not compromise the anti-tumor efficacy of cisplatin.Cisplatin, a widely used and effective cancer chemotherapeutic agent, is known for its nephrotoxicity, which can lead to acute kidney injury (AKI) in up to 30% of patients. This review discusses recent advances in understanding the cellular mechanisms underlying cisplatin-induced renal cell death and the role of inflammation in exacerbating kidney injury. Cisplatin accumulation in the kidney is facilitated by transporters such as Ctrl and OCT2, leading to DNA and mitochondrial damage. Apoptotic pathways, including intrinsic and extrinsic pathways, are activated, contributing to renal epithelial cell death. Inflammation, mediated by cytokines like TNF-α and toll-like receptors (TLRs), plays a crucial role in amplifying kidney injury. The review also explores preventive strategies, including volume expansion, amifostine, and targeting cisplatin uptake and inflammation, highlighting the need for careful evaluation of these strategies to ensure they do not compromise the anti-tumor efficacy of cisplatin.