The article reviews the current understanding of major depressive disorder (MDD), its pathogenesis, diagnosis, prevention, and treatment. MDD is a significant global health issue, affecting millions worldwide and causing substantial economic and social burdens. The complex and multifaceted nature of MDD's pathogenesis has led to the development of various hypotheses, including the neurotransmitter and receptor hypothesis, the hypothalamic-pituitary-adrenal (HPA) axis hypothesis, the cytokine hypothesis, the neuroplasticity hypothesis, and the systemic influence hypothesis. However, these hypotheses alone cannot fully explain the disease, and recent research has highlighted the importance of multiple organ interactions and multitarget modulatory strategies. The article discusses the role of genetic, environmental, and social factors in the development of MDD. Genetic factors, such as variations in genes related to neurotransmitter systems, play a crucial role, while environmental stressors and comorbidities also contribute significantly. The HPA axis hypothesis emphasizes the impact of stress on MDD, with hyperactivity of the HPA axis leading to neuroendocrine imbalances and cognitive and emotional changes. The cytokine hypothesis highlights the role of inflammation, with proinflammatory cytokines contributing to the pathogenesis of MDD. Recent studies have also explored the role of astrocytes in MDD, suggesting that astrocytic dysfunction is a key factor. Astrocytes, which are essential regulators of neurotransmitter systems, can influence the release and clearance of neurotransmitters like serotonin, norepinephrine, and dopamine. The article details the pharmacological mechanisms of antidepressants, such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), and their effects on astrocytes. Additionally, the article reviews the potential of novel therapeutic approaches, including phototherapy and acupuncture, which have shown effective improvements in depressive symptoms. The review also discusses the latest research on the pathogenesis of MDD, emphasizing the need for a comprehensive understanding of the interactions between multiple cells and organs to better understand and treat the disorder.The article reviews the current understanding of major depressive disorder (MDD), its pathogenesis, diagnosis, prevention, and treatment. MDD is a significant global health issue, affecting millions worldwide and causing substantial economic and social burdens. The complex and multifaceted nature of MDD's pathogenesis has led to the development of various hypotheses, including the neurotransmitter and receptor hypothesis, the hypothalamic-pituitary-adrenal (HPA) axis hypothesis, the cytokine hypothesis, the neuroplasticity hypothesis, and the systemic influence hypothesis. However, these hypotheses alone cannot fully explain the disease, and recent research has highlighted the importance of multiple organ interactions and multitarget modulatory strategies. The article discusses the role of genetic, environmental, and social factors in the development of MDD. Genetic factors, such as variations in genes related to neurotransmitter systems, play a crucial role, while environmental stressors and comorbidities also contribute significantly. The HPA axis hypothesis emphasizes the impact of stress on MDD, with hyperactivity of the HPA axis leading to neuroendocrine imbalances and cognitive and emotional changes. The cytokine hypothesis highlights the role of inflammation, with proinflammatory cytokines contributing to the pathogenesis of MDD. Recent studies have also explored the role of astrocytes in MDD, suggesting that astrocytic dysfunction is a key factor. Astrocytes, which are essential regulators of neurotransmitter systems, can influence the release and clearance of neurotransmitters like serotonin, norepinephrine, and dopamine. The article details the pharmacological mechanisms of antidepressants, such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs), and their effects on astrocytes. Additionally, the article reviews the potential of novel therapeutic approaches, including phototherapy and acupuncture, which have shown effective improvements in depressive symptoms. The review also discusses the latest research on the pathogenesis of MDD, emphasizing the need for a comprehensive understanding of the interactions between multiple cells and organs to better understand and treat the disorder.