Photobiomodulation (PBM) therapy, which employs red to near-infrared (NIR) light, has emerged as a promising approach to treat various neurological and psychological disorders. The mechanism involves activating cytochrome c oxidase in the mitochondrial respiratory chain, enhancing ATP synthesis, and triggering calcium ion release through light absorption by ion channels. This process not only boosts neuronal metabolic capacity but also promotes anti-oxidant, anti-inflammatory, and anti-apoptotic responses, fostering neurogenesis and synaptogenesis. PBM shows potential in treating conditions like dementia, stroke, brain trauma, Parkinson’s disease, and depression, and even enhancing cognitive functions in healthy individuals. However, delivering sufficient light to the brain through transcranial approaches is challenging due to limited tissue penetration. Alternative delivery methods, such as intracranial and intranasal approaches, are being explored to overcome this issue. This review aims to explore the mechanisms of PBM and provide a summary of preclinical investigations and clinical trials, highlighting its potential as a therapeutic modality for various brain disorders. The review covers the molecular mechanisms underlying PBM, including the role of cytochrome c oxidase, light/heat-sensitive ion channels, and retrograde mitochondrial signaling. It also discusses current strategies for delivering light to different brain regions, such as transcranial, intracranial, and intranasal approaches, and the depth of light penetration and sources of light. The neurobiological consequences of PBM therapy are detailed, including its effects on neuronal bioenergetics, cerebral blood flow and angiogenesis, oxidative stress, neuroinflammatory suppression, anti-apoptosis and neuroprotection, neurogenesis and synaptogenesis, and impacts on intrinsic brain networks. The review also explores the systemic effects of PBM therapy and its clinical applications, including stroke, traumatic brain injury, Alzheimer’s disease, Parkinson’s disease, depression, and cognitive improvement in healthy subjects. In conclusion, PBM therapy shows significant promise in neuroscience, offering a non-invasive and potentially effective approach to treat a wide range of brain disorders and enhance cognitive functions. Further research is needed to optimize delivery methods and expand its therapeutic applications.Photobiomodulation (PBM) therapy, which employs red to near-infrared (NIR) light, has emerged as a promising approach to treat various neurological and psychological disorders. The mechanism involves activating cytochrome c oxidase in the mitochondrial respiratory chain, enhancing ATP synthesis, and triggering calcium ion release through light absorption by ion channels. This process not only boosts neuronal metabolic capacity but also promotes anti-oxidant, anti-inflammatory, and anti-apoptotic responses, fostering neurogenesis and synaptogenesis. PBM shows potential in treating conditions like dementia, stroke, brain trauma, Parkinson’s disease, and depression, and even enhancing cognitive functions in healthy individuals. However, delivering sufficient light to the brain through transcranial approaches is challenging due to limited tissue penetration. Alternative delivery methods, such as intracranial and intranasal approaches, are being explored to overcome this issue. This review aims to explore the mechanisms of PBM and provide a summary of preclinical investigations and clinical trials, highlighting its potential as a therapeutic modality for various brain disorders. The review covers the molecular mechanisms underlying PBM, including the role of cytochrome c oxidase, light/heat-sensitive ion channels, and retrograde mitochondrial signaling. It also discusses current strategies for delivering light to different brain regions, such as transcranial, intracranial, and intranasal approaches, and the depth of light penetration and sources of light. The neurobiological consequences of PBM therapy are detailed, including its effects on neuronal bioenergetics, cerebral blood flow and angiogenesis, oxidative stress, neuroinflammatory suppression, anti-apoptosis and neuroprotection, neurogenesis and synaptogenesis, and impacts on intrinsic brain networks. The review also explores the systemic effects of PBM therapy and its clinical applications, including stroke, traumatic brain injury, Alzheimer’s disease, Parkinson’s disease, depression, and cognitive improvement in healthy subjects. In conclusion, PBM therapy shows significant promise in neuroscience, offering a non-invasive and potentially effective approach to treat a wide range of brain disorders and enhance cognitive functions. Further research is needed to optimize delivery methods and expand its therapeutic applications.