Brain-Derived Neurotrophic Factor (BDNF) is a key growth factor in the central nervous system (CNS), essential for CNS development and neuronal plasticity. It plays a crucial role in psychiatric diseases, including major depressive disorder (MDD), schizophrenia, bipolar disorder, anxiety-related disorders, and addiction. This review summarizes clinical and preclinical evidence on BDNF's involvement in these conditions and its potential as a therapeutic target. BDNF signaling occurs through TrkB receptors and influences synaptic plasticity, neuronal survival, and neurotransmitter systems. It is involved in the development and function of neurons, particularly in dopaminergic, GABAergic, cholinergic, and serotonergic systems. BDNF is also crucial for learning, memory, and synaptic plasticity, and its dysregulation is linked to neuropsychiatric disorders. In MDD, BDNF levels are reduced by stress and depression but increased by antidepressants. BDNF expression is decreased in the hippocampus and prefrontal cortex in MDD patients, while it is increased in the nucleus accumbens and amygdala. BDNF deficiency in animal models leads to impaired antidepressant responses, suggesting its role in antidepressant efficacy. BDNF polymorphisms, such as the V66M variant, are associated with increased risk for MDD and may influence susceptibility to stress-induced depression. In bipolar disorder, BDNF levels are altered in postmortem brain tissue, and the V66M allele is strongly correlated with BD. BDNF is also involved in anxiety-related disorders, with studies showing that BDNF polymorphisms may influence anxiety-related behaviors. In PTSD, BDNF is implicated in fear memory formation and extinction, and BDNF agonists may have therapeutic potential. In schizophrenia, BDNF levels are altered in brain regions such as the frontal cortex and hippocampus, and antipsychotic drugs have varying effects on BDNF expression. Animal models of schizophrenia, including neonatal ventral hippocampal lesions, gestational MAM exposure, and long-term amphetamine administration, show altered BDNF levels, suggesting a role in disease pathology. BDNF is also involved in neurodevelopmental disorders such as Rett syndrome and Rubinstein-Taybi syndrome, and in eating disorders. BDNF-based therapies, including BDNF mimetics, are being explored for their potential in treating these conditions. Overall, BDNF plays a critical role in neuropsychiatric disorders, and its regulation is essential for normal brain function and behavior. Further research is needed to fully understand BDNF's mechanisms and its potential as a therapeutic target.Brain-Derived Neurotrophic Factor (BDNF) is a key growth factor in the central nervous system (CNS), essential for CNS development and neuronal plasticity. It plays a crucial role in psychiatric diseases, including major depressive disorder (MDD), schizophrenia, bipolar disorder, anxiety-related disorders, and addiction. This review summarizes clinical and preclinical evidence on BDNF's involvement in these conditions and its potential as a therapeutic target. BDNF signaling occurs through TrkB receptors and influences synaptic plasticity, neuronal survival, and neurotransmitter systems. It is involved in the development and function of neurons, particularly in dopaminergic, GABAergic, cholinergic, and serotonergic systems. BDNF is also crucial for learning, memory, and synaptic plasticity, and its dysregulation is linked to neuropsychiatric disorders. In MDD, BDNF levels are reduced by stress and depression but increased by antidepressants. BDNF expression is decreased in the hippocampus and prefrontal cortex in MDD patients, while it is increased in the nucleus accumbens and amygdala. BDNF deficiency in animal models leads to impaired antidepressant responses, suggesting its role in antidepressant efficacy. BDNF polymorphisms, such as the V66M variant, are associated with increased risk for MDD and may influence susceptibility to stress-induced depression. In bipolar disorder, BDNF levels are altered in postmortem brain tissue, and the V66M allele is strongly correlated with BD. BDNF is also involved in anxiety-related disorders, with studies showing that BDNF polymorphisms may influence anxiety-related behaviors. In PTSD, BDNF is implicated in fear memory formation and extinction, and BDNF agonists may have therapeutic potential. In schizophrenia, BDNF levels are altered in brain regions such as the frontal cortex and hippocampus, and antipsychotic drugs have varying effects on BDNF expression. Animal models of schizophrenia, including neonatal ventral hippocampal lesions, gestational MAM exposure, and long-term amphetamine administration, show altered BDNF levels, suggesting a role in disease pathology. BDNF is also involved in neurodevelopmental disorders such as Rett syndrome and Rubinstein-Taybi syndrome, and in eating disorders. BDNF-based therapies, including BDNF mimetics, are being explored for their potential in treating these conditions. Overall, BDNF plays a critical role in neuropsychiatric disorders, and its regulation is essential for normal brain function and behavior. Further research is needed to fully understand BDNF's mechanisms and its potential as a therapeutic target.