Background <p>Photobiomodulation therapy (PBMT) represents a rapidly expanding area of translational research that bridges photophysics, mitochondrial biology, and clinical rehabilitation. It leverages low-level light to modulate cellular bioenergetics, inflammatory signaling, and tissue repair processes across various medical disciplines.</p> Methods <p>A systematic literature search was conducted using Google Scholar, Scopus, PubMed, and Web of Science to identify recent clinical and mechanistic studies on PBMT. The gathered evidence was analyzed to evaluate the influence of PBMT on cytochrome c oxidase–mediated energy transduction, reactive oxygen species modulation, nitric oxide signaling, and cytokine regulation.</p> Results <p>Current findings indicate that PBMT exerts multifaceted effects on metabolism and immune homeostasis. Clinical applications have expanded from dermatology and wound healing to musculoskeletal, neurological, ophthalmic, and oncologic conditions. PBMT shows potential for symptom alleviation, accelerated recovery, and tissue protection under oxidative or inflammatory stress. However, translation from preclinical evidence to consistent clinical outcomes remains constrained by non-standardized dosimetry, inconsistent energy delivery, and heterogeneous study endpoints. Negative or equivocal outcomes in trials involving trained or low-stress cohorts highlight the context-dependent efficacy of PBMT. Immunoregulatory insights further reveal links between redox-sensitive transcriptional control and systemic cytokine balance.</p> Conclusions <p>By integrating mechanistic and clinical perspectives, this review positions PBMT as a promising yet incompletely optimized platform for mechanism-guided phototherapy. Future directions include biomarker-guided treatment monitoring, advanced device engineering, and personalized PBMT modeling through optical and metabolic profiling to achieve its full translational and therapeutic potential.</p>