This review discusses the neurocircuitry underlying mood disorders, focusing on the limbic system, including the amygdala, hippocampus, and prefrontal cortex. It begins with a historical overview of early studies on the limbic system's role in emotion, followed by detailed descriptions of neural circuits linking specific structures involved in mood disorders. These circuits connect the medial prefrontal cortex, amygdala, ventromedial striatum, medial thalamus, hypothalamus, and brainstem. Human data from neuroimaging, lesion analysis, and histological studies indicate that these circuits are central to mood disorders. The review outlines the neural systems involved in mood disorders, divided into two sections: neuroanatomy of circuits in non-human primates and human observations. It discusses the limbic system's role in emotion, including the amygdala's involvement in emotional processing and the medial prefrontal cortex's role in emotional regulation. The review also describes the connections between the medial prefrontal cortex and other brain regions, such as the striatum, thalamus, and hypothalamus, and how these connections are involved in mood disorders. The review highlights the orbital and medial prefrontal cortex (OMPFC) as key regions in mood disorders. The orbital network is involved in sensory processing, while the medial network is more involved in emotional regulation and visceral control. The review also discusses the lateral prefrontal cortex (LPFC) and its connections to the medial and orbital networks. The review describes the cortico-striato-pallido-thalamic circuits related to the OMPFC and their role in mood disorders. The review also discusses the connections between the prefrontal cortex and the hypothalamus and brainstem, which are involved in visceral functions. It describes the role of the medial prefrontal network in emotional processing and its connections to the hypothalamus and periaqueductal gray. The review also discusses the role of the medial prefrontal network in the 'somatic marker hypothesis,' which suggests that visceral reactions serve as subconscious guides for behavior. The review discusses the neuroimaging abnormalities in mood disorders, including reduced gray matter volume in the subgenual anterior cingulate cortex (sgACC) and other regions. It also discusses the role of the hypothalamic-pituitary-adrenal (HPA) axis in mood disorders and how its dysfunction may contribute to the symptoms of depression and bipolar disorder. The review concludes that the neural circuits involved in mood disorders are complex and involve multiple brain regions, and that understanding these circuits is essential for developing effective treatments for mood disorders.This review discusses the neurocircuitry underlying mood disorders, focusing on the limbic system, including the amygdala, hippocampus, and prefrontal cortex. It begins with a historical overview of early studies on the limbic system's role in emotion, followed by detailed descriptions of neural circuits linking specific structures involved in mood disorders. These circuits connect the medial prefrontal cortex, amygdala, ventromedial striatum, medial thalamus, hypothalamus, and brainstem. Human data from neuroimaging, lesion analysis, and histological studies indicate that these circuits are central to mood disorders. The review outlines the neural systems involved in mood disorders, divided into two sections: neuroanatomy of circuits in non-human primates and human observations. It discusses the limbic system's role in emotion, including the amygdala's involvement in emotional processing and the medial prefrontal cortex's role in emotional regulation. The review also describes the connections between the medial prefrontal cortex and other brain regions, such as the striatum, thalamus, and hypothalamus, and how these connections are involved in mood disorders. The review highlights the orbital and medial prefrontal cortex (OMPFC) as key regions in mood disorders. The orbital network is involved in sensory processing, while the medial network is more involved in emotional regulation and visceral control. The review also discusses the lateral prefrontal cortex (LPFC) and its connections to the medial and orbital networks. The review describes the cortico-striato-pallido-thalamic circuits related to the OMPFC and their role in mood disorders. The review also discusses the connections between the prefrontal cortex and the hypothalamus and brainstem, which are involved in visceral functions. It describes the role of the medial prefrontal network in emotional processing and its connections to the hypothalamus and periaqueductal gray. The review also discusses the role of the medial prefrontal network in the 'somatic marker hypothesis,' which suggests that visceral reactions serve as subconscious guides for behavior. The review discusses the neuroimaging abnormalities in mood disorders, including reduced gray matter volume in the subgenual anterior cingulate cortex (sgACC) and other regions. It also discusses the role of the hypothalamic-pituitary-adrenal (HPA) axis in mood disorders and how its dysfunction may contribute to the symptoms of depression and bipolar disorder. The review concludes that the neural circuits involved in mood disorders are complex and involve multiple brain regions, and that understanding these circuits is essential for developing effective treatments for mood disorders.