Application of allostatic theory to stress during the 1990s refocused attention on internal responses to a perceived hazard, and the last 20 years has seen considerable developments in the biological contexts of stress. Evidence from neuroscience now suggests that secretion of the hormone cortisol is not only stimulated by the outcomes of cognitive transaction but it also feeds back and contributes positively to the cognitive adaptation that is a feature of stress resilience. More recently, the operative intracellular mechanisms are beginning to be understood and provide an insight into the regulation and maintenance of intracellular homeostasis that underpins adaptive change and vulnerability. The maintenance or appropriate modulation of intracellular homeostasis usually provides a buffering of potential adverse interactions. However, the capacity to do so is diminished during chronic stress leading to intracellular and subsequently systemic, homeostatic failure and hence maladaptation. This area of research seems far removed from cognitive theory, but placing intracellular homeostasis at the core of cognitive and biological responses supports the concept of stress as a genuinely psycho-biological phenomenon.