Depression is a prevalent mental health condition worldwide and is the leading cause of disability in adults under the age of 45. Most individuals with major depressive disorder (MDD) report only a 50% decrease in symptoms with the use of the standard allopathic treatments for depression. The mechanisms underlying depression remain poorly understood even though stress and its correlates contribute to multiple aspects of the phenomenology of depression. Thus, stress and depression are clearly linked, as stress may precipitate or exacerbate depressive symptoms and depression may be a cause and/or outcome of acute or chronic stress. Therefore, use of additional therapeutic approaches to address stress and depression, such as complementary therapies including yoga, may contribute importantly to symptom reduction. Based on an emerging picture of how stress and mood are regulated within the nervous system, and considering the Executive Homeostatic Network concept that we have recently advanced, we provide an integrative overview of biological mechanisms and substrates that may mediate depression, which should be targets for research to evaluate how the practice of yoga can mitigate depressive symptomatology.