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The aging of the population and the increasing prevalence of multimorbidity contribute to the widespread use of polypharmacotherapy, which in turn elevates the risk of adverse drug reactions and clinically significant drug–drug interactions. One of the key yet frequently underestimated issues in clinical practice is the prescribing cascade, which occurs when an adverse drug reaction is misinterpreted as a new medical condition, leading to the initiation of an additional medication. This phenomenon is particularly relevant in the older population, in whom altered pharmacokinetics and pharmacodynamics, together with reduced organ reserve, increase susceptibility to adverse drug events, including nephrotoxicity (renal impairment is used throughout the review as a clinically relevant example of organ-specific harm resulting from prescribing cascades, rather than as the sole focus of the analysis). This article discusses the mechanisms and clinical consequences of the prescribing cascade—with particular emphasis on renal function deterioration—as well as strategies for its prevention in the geriatric population. Analysis of the literature indicates that prescribing cascades remain insufficiently recognized in clinical practice, despite the availability of pharmacotherapy assessment tools such as The American Geriatrics Society (AGS) Beers Criteria and the STOPP/START criteria. Documented prescribing cascades have been shown to contribute to deterioration in health status and quality of life, an increased frequency of hospitalizations, and a greater burden on healthcare systems. Particularly concerning are cascades involving cardiovascular, neurological, and analgesic medications, which may induce or exacerbate renal injury, ultimately leading to chronic kidney disease and organ failure. Prescribing cascades represent a significant yet frequently underestimated threat to the efficacy and safety of pharmacotherapy in older adults. Their consequences may extend beyond reduced quality of life and increased treatment costs to include serious complications such as the development of renal failure. Enhancing clinicians’ awareness, conducting systematic medication reviews, and employing validated assessment tools are essential for the identification and prevention of prescribing cascades, thereby reducing the risk of renal injury and improving clinical outcomes.