Evidence suggests that chronic stress affects the hypothalamic-pituitary-adrenal (HPA) axis and plays an important role in the pathogenesis of depression. In this short article we describe the link between chron¬ic stress, hypothalamic-pituitary-adrenal axis abnormalities, sleep disturbance, metabolic abnormalities and depression. We also discuss how hair cortisol measurements can be used as a biomarker of chronic stress. We also suggest that hair cortisol measurements can also be used to monitor improvement as a result of treatments such as antidepressants and mindfulness.