In this overview, we summarize findings on hypothalamus-pituitary-adrenal (HPA) axis functioning in burned out and (vitally) exhausted though otherwise healthy subjects as well as clinically diagnosed patients. The main focus will be on basal diurnal free cortisol regulation and cortisol responses to acute psychological stress. First, we describe normal HPA axis regulation as well as dysfunction which manifests in hyper- or hypoactivity. We also briefly illustrate three established methods to assess HPA axis activity, reactivity, and feedback functioning, namely the cortisol awakening rise (CAR), Trier Social Stress Test (TSST), and low-dose Dexamethasone Suppression Test (DST). Then, an up-to-date summary of empirical findings on the relationship between burnout, respectively vital exhaustion, and cortisol is provided including field as well as laboratory studies. Finally, we briefly discuss possible methodologically confounders and speculate on underlying mechanisms explaining, at least in part, how burnout and vital exhaustion might relate to disease vulnerability.