The article reviews the growing body of evidence that links the immune system to brain function and behavior, particularly in the context of inflammation. Pro-inflammatory cytokines can access the central nervous system (CNS) and interact with a cytokine network in the brain, influencing various aspects of brain function related to behavior, including neurotransmitter metabolism, neuroendocrine function, synaptic plasticity, and neurocircuits regulating mood, motor activity, motivation, anxiety, and alarm. Behavioral consequences of these immune-driven effects include depression, anxiety, fatigue, psychomotor slowing, anorexia, cognitive dysfunction, and sleep impairment, which overlap with symptoms of neuropsychiatric disorders, especially depression. Key pathways involved include cytokine signaling molecules (p38 mitogen-activated protein kinase and nuclear factor kappa B), indoleamine 2,3-dioxygenase and its downstream metabolites (kynurenine, quinolinic acid, and kynurenic acid), neurotransmitters (serotonin, dopamine, and glutamate), and neurocircuits involving the basal ganglia and anterior cingulate cortex. Vulnerability factors such as aging, obesity, and chronic stress interact with immune-to-brain signaling to exacerbate immunologic contributions to neuropsychiatric disease. Understanding these mechanisms provides targets for potential therapeutic development and strategies for preventing neuropsychiatric disorders in at-risk populations.The article reviews the growing body of evidence that links the immune system to brain function and behavior, particularly in the context of inflammation. Pro-inflammatory cytokines can access the central nervous system (CNS) and interact with a cytokine network in the brain, influencing various aspects of brain function related to behavior, including neurotransmitter metabolism, neuroendocrine function, synaptic plasticity, and neurocircuits regulating mood, motor activity, motivation, anxiety, and alarm. Behavioral consequences of these immune-driven effects include depression, anxiety, fatigue, psychomotor slowing, anorexia, cognitive dysfunction, and sleep impairment, which overlap with symptoms of neuropsychiatric disorders, especially depression. Key pathways involved include cytokine signaling molecules (p38 mitogen-activated protein kinase and nuclear factor kappa B), indoleamine 2,3-dioxygenase and its downstream metabolites (kynurenine, quinolinic acid, and kynurenic acid), neurotransmitters (serotonin, dopamine, and glutamate), and neurocircuits involving the basal ganglia and anterior cingulate cortex. Vulnerability factors such as aging, obesity, and chronic stress interact with immune-to-brain signaling to exacerbate immunologic contributions to neuropsychiatric disease. Understanding these mechanisms provides targets for potential therapeutic development and strategies for preventing neuropsychiatric disorders in at-risk populations.