This is a review on the topic of work-related stress (WRS), and how difficulities with differential diagnostics often arise because of overlapping symptoms between WRS and depression. Investigation into the hypothalamic-pituitary-adrenal (HPA) axis deviations seems to reveal the HPA axis as a promising biomarker, since studies have shown, that patients with melancholic type depression exhibit hyper-cortisolism, while patients with WRS exhibit hypocortisolism. More studies of better quality are needed, before anything conclusive can be said. Consensus regarding definition and a development of diagnostic criteria for WRS, e.g. the Swedish "exhaustion disorder", could enable a better differentiation and contribute to more accurate treatment and research.