Abstract
<jats:p>Ultraweak photon emission (UPE), also known as biological autoluminescence or biophoton, is a ubiquitous but exceptionally faint optical signature of living systems, generated primarily from electronically excited species during oxidative and metabolic reactions. Despite nearly a century of investigation, the field remains caught between established photochemistry and unresolved claims of broader biological function. Progress is constrained by photon fluxes near detector noise floors, heterogeneous acquisition and analysis protocols, limited reproducibility across laboratories, and the difficulty of disentangling overlapping biochemical sources from potentially structured biological dynamics. These limitations have prevented UPE from becoming a mature quantitative modality and continue to complicate claims concerning coherence, long-range correlations, and photon-mediated signalling. Yet the technological landscape is changing rapidly. Advances in quantum-limited single-photon detectors, low-noise imaging, spectral and correlation measurements, integrated photonics, and artificial intelligence now provide opportunities to test long-standing hypotheses with substantially greater rigor and to extract information from photon-starved biological signals. Here, we critically reassess the historical development, biochemical foundations, measurement technologies, and biological interpretation of UPE, distinguishing robust evidence from unresolved controversy. We identify standardization, mechanistic attribution, multimodal validation, and clinically meaningful benchmarking as central priorities, while highlighting emerging opportunities in non-invasive diagnostics, wearable sensing, bio-inspired materials, and AI-assisted analysis. We argue that the future of UPE depends less on expanding speculative interpretations than on converting an intriguing endogenous emission into a reproducible, mechanistically grounded, and predictive measurement science at the interface of biology, photonics, and medicine.</jats:p>