The article reviews the role of inflammation in central nervous system (CNS) injury and disease. It highlights that while the CNS was once considered immune-privileged, it now exhibits features of inflammation, with resident cells generating inflammatory mediators in response to injury, infection, or disease. These mediators, including cytokines, prostaglandins, free radicals, and complement, induce chemokines and adhesion molecules, recruit immune cells, and activate glial cells. The review discusses the evidence that inflammation contributes to acute, chronic, and psychiatric CNS disorders, noting that inflammatory mediators can have both detrimental and beneficial effects, complicating their use as novel therapies. The article also explores the complex interplay between inflammatory mediators, aging, genetic background, and environmental factors, which may regulate the outcome of acute CNS injury and the progression of chronic neurodegeneration. Finally, it suggests that combination therapies, targeting multiple inflammatory pathways, may be the most effective approach for treating CNS diseases.The article reviews the role of inflammation in central nervous system (CNS) injury and disease. It highlights that while the CNS was once considered immune-privileged, it now exhibits features of inflammation, with resident cells generating inflammatory mediators in response to injury, infection, or disease. These mediators, including cytokines, prostaglandins, free radicals, and complement, induce chemokines and adhesion molecules, recruit immune cells, and activate glial cells. The review discusses the evidence that inflammation contributes to acute, chronic, and psychiatric CNS disorders, noting that inflammatory mediators can have both detrimental and beneficial effects, complicating their use as novel therapies. The article also explores the complex interplay between inflammatory mediators, aging, genetic background, and environmental factors, which may regulate the outcome of acute CNS injury and the progression of chronic neurodegeneration. Finally, it suggests that combination therapies, targeting multiple inflammatory pathways, may be the most effective approach for treating CNS diseases.