Purpose of Review <p>Mood disorders during perimenopause and menopause are very common but often underdiagnosed, significantly affecting quality of life and well-being. Women face higher risks of depression and anxiety, with depressive symptoms typically more severe during the transition than before or after menopause. Menopausal depression has a complex etiology, and this review aims to explore the etiology and pathogenesis of depression during this vulnerable stage of life while focusing on the latest evidence.</p> Recent Findings <p>Fluctuations in estrogens and progesterone, dysregulation of the hypothalamic-pituitary-adrenal axis, changes in neurochemical systems, alterations in circadian rhythm, and endogenous opioid dysregulation are key disease mechanisms that have been traditionally described. Genetic predisposition and life stressors are additional contributing factors. Recent research points toward structural brain changes, neuroinflammatory processes and oxidative stress mechanisms as possible causes. Including biomarkers such as neuroinflammatory markers and oxidative stress indices could aid in risk stratification and guide personalized treatment plans.</p> Summary <p>This review summarizes current understanding of the etiopathogenesis of menopausal depression, emphasizing hormonal, neurobiological, inflammatory, and psychosocial factors, along with promising evidence-based treatments including pharmacologic, hormonal, and non-pharmacologic therapies.</p>