For centuries, physicians relied on their senses, including smell, to identify disease. Distinct odors associated with conditions such as diabetes, liver disease, infections, and metabolic disorders often provided valuable clinical clues long before laboratory tests existed. With the rise of modern analytical technologies, however, olfactory diagnosis largely disappeared from mainstream medicine. A recent review by J. E. Hayes and colleagues challenges this trend, arguing that olfaction remains an underutilized yet powerful diagnostic tool with significant potential for future healthcare applications.

The review, Olfaction as a Diagnostic Instrument: A Review of Current and Future Medical Applications, highlights how the human olfactory system evolved to detect volatile organic compounds (VOCs), the chemical signatures continuously released by biological processes. Many diseases alter metabolism, inflammation, or microbial activity, leading to changes in VOC production. These odor signatures can become detectable in breath, sweat, urine, skin emissions, or other biological samples, creating a chemical fingerprint of health status. According to the authors, analyzing these olfactory signals may provide a rapid, non-invasive, and cost-effective means of detecting disease.

The COVID-19 pandemic brought renewed attention to the diagnostic potential of smell. During the global search for rapid testing strategies, researchers explored the use of trained detection dogs capable of recognizing odor patterns associated with SARS-CoV-2 infection. Although large-scale clinical implementation remained limited, these efforts demonstrated that disease-specific odor signatures can be detected with remarkable sensitivity and specificity when appropriate methodologies are applied. The review notes that the pandemic served as a powerful reminder that olfactory approaches may complement conventional diagnostic technologies, particularly when rapid screening is required.

Importantly, the authors emphasize that olfactory diagnosis is not restricted to humans. Dogs are perhaps the most well-known biological detectors due to their extraordinary olfactory capabilities, but other animals may also contribute to disease detection under specific circumstances. Human assessors, trained animal detectors, and technological systems designed to mimic biological olfaction all represent potential avenues for future diagnostic development. The key challenge lies in establishing rigorous protocols, standardization, and validation frameworks that ensure reliability and reproducibility across clinical settings.

One of the most compelling aspects of olfactory diagnostics is its practicality. Unlike many modern medical tests that require specialized equipment, laboratory infrastructure, or invasive procedures, odor-based approaches could potentially offer high diagnostic performance at relatively low cost, while minimizing patient discomfort and reducing turnaround time. Such characteristics could be particularly valuable in resource-limited environments, population-level screening programs, and early disease detection initiatives.

The review ultimately envisions a future where smell-based diagnostics are integrated with advances in analytical chemistry, sensor technologies, artificial intelligence, and precision medicine. Rather than replacing existing diagnostic tools, olfactory methods may serve as rapid frontline screening systems capable of identifying individuals who require further clinical evaluation. As research continues to uncover the complex relationship between disease processes and odor signatures, the scent profile of a patient may become an increasingly important source of medical information.

The message is clear: far from being an outdated clinical curiosity, olfaction may represent one of the most accessible, non-invasive, and biologically informative diagnostic modalities available. As scientists continue to decode the language of volatile organic compounds, the future of healthcare may quite literally depend on what we can smell.

Reference: Hayes JE, Hayes SA, Wilkins D, Lindley MR, Stuetz RM. Olfaction as a Diagnostic Instrument: A Review of Current and Future Medical Applications. Talanta (2026), PMID: 42424887.