Stress is one of the most significant health problems in modern societies and the 21st century. This explains a pressing need for investigations into the biological pathways linking stress and health. Besides the locus coeruleus-noradrenaline/autonomic (sympathetic) nervous system ( Chrousos and Gold 1992 ), the hypothalamus-pituitary-adrenal (HPA) axis is the major physiological stress response system in the body. Since alterations in HPA axis regulation under basal conditions and in response to acute stress appear to be a close correlate or even a determining factor of the onset of different diseases or disease progression ( Holsboer 1989 ; Chrousos and Gold 1992 ; Tsigos and Chrousos 1994, 2002 ; Stratakis and Chrousos 1995 ; McEwen 1998 ; Heim et al. 2000a ; Raison and Miller 2003 ), the characterization of an individual's HPA axis activity as well as reactivity pattern to psychosocial stress appears to be of major interest. It is obvious that such a research agenda substantially depends on the availability of appropriate measures. However, since the HPA axis is a highly adaptive system which is characterized by marked inter- and intraindividual variability ( Mason 1968 ; Hellhammer et al. 2009 ), the development of such markers of HPA axis regulation in humans was-and still is-a rather challenging task. In this brief review, we focus on findings on two HPA axis measures, namely the cortisol-awakening response (CAR) to assess HPA axis basal activity and the Trier social stress test (TSST) to investigate HPA axis stress reactivity.