Photobiomodulation (PBM) or low-level light therapy (LLLT) has been studied for nearly 50 years but has not gained widespread acceptance due to uncertainties about its molecular, cellular, and tissue mechanisms. Recent research has provided valuable insights into these mechanisms. Cytochrome c oxidase (Cox), a key enzyme in the mitochondrial respiratory chain, is a significant chromophore in PBM. The leading hypothesis suggests that photons dissociate inhibitory nitric oxide from Cox, increasing electron transport, mitochondrial membrane potential, and ATP production. Another hypothesis involves light-sensitive ion channels that allow calcium entry into cells. After photon absorption, numerous signaling pathways are activated, leading to the activation of transcription factors and the upregulation of genes related to protein synthesis, cell migration, proliferation, anti-inflammatory signaling, and antioxidant enzymes. Stem and progenitor cells are particularly responsive to LLLT. The parameters of PBM, such as light source and dose, are crucial. Low-power light sources (below 500 mW) are used to promote tissue repair, reduce inflammation, and provide analgesia without causing significant temperature changes. The biphasic dose response curve, following the Arndt-Schulz Law, indicates that both too low and too high doses can be ineffective or even harmful. Proper parameter selection is essential for optimal results. Molecular mechanisms of PBM include the activation of Cox, which increases electron transport and ATP production. PBM also increases cAMP levels, activates transcription factors like NF-κB, and modulates reactive oxygen species (ROS). Changes in mitochondrial ultrastructure can alter Ca2+ concentration, affecting signaling pathways. PBM can also influence the RANKL/OPG ratio, HIF-1α activity, and the AKT/GSK3β/β-catenin pathway, among others. Effector molecules such as TGF-β, VEGF, and HSPs play important roles in wound healing, angiogenesis, and anti-inflammatory responses. PBM can modulate these molecules to promote healing and reduce inflammation. In conclusion, PBM's mechanisms involve chromophores, signaling molecules, transcription factors, and effector molecules, with specific pathways and effects on different tissues and cells. Proper parameter selection and understanding of these mechanisms are key to optimizing PBM's therapeutic applications.Photobiomodulation (PBM) or low-level light therapy (LLLT) has been studied for nearly 50 years but has not gained widespread acceptance due to uncertainties about its molecular, cellular, and tissue mechanisms. Recent research has provided valuable insights into these mechanisms. Cytochrome c oxidase (Cox), a key enzyme in the mitochondrial respiratory chain, is a significant chromophore in PBM. The leading hypothesis suggests that photons dissociate inhibitory nitric oxide from Cox, increasing electron transport, mitochondrial membrane potential, and ATP production. Another hypothesis involves light-sensitive ion channels that allow calcium entry into cells. After photon absorption, numerous signaling pathways are activated, leading to the activation of transcription factors and the upregulation of genes related to protein synthesis, cell migration, proliferation, anti-inflammatory signaling, and antioxidant enzymes. Stem and progenitor cells are particularly responsive to LLLT. The parameters of PBM, such as light source and dose, are crucial. Low-power light sources (below 500 mW) are used to promote tissue repair, reduce inflammation, and provide analgesia without causing significant temperature changes. The biphasic dose response curve, following the Arndt-Schulz Law, indicates that both too low and too high doses can be ineffective or even harmful. Proper parameter selection is essential for optimal results. Molecular mechanisms of PBM include the activation of Cox, which increases electron transport and ATP production. PBM also increases cAMP levels, activates transcription factors like NF-κB, and modulates reactive oxygen species (ROS). Changes in mitochondrial ultrastructure can alter Ca2+ concentration, affecting signaling pathways. PBM can also influence the RANKL/OPG ratio, HIF-1α activity, and the AKT/GSK3β/β-catenin pathway, among others. Effector molecules such as TGF-β, VEGF, and HSPs play important roles in wound healing, angiogenesis, and anti-inflammatory responses. PBM can modulate these molecules to promote healing and reduce inflammation. In conclusion, PBM's mechanisms involve chromophores, signaling molecules, transcription factors, and effector molecules, with specific pathways and effects on different tissues and cells. Proper parameter selection and understanding of these mechanisms are key to optimizing PBM's therapeutic applications.