Psychological stress can lead to the dysregulation of core physiological systems including the sympathetic-adrenal-medullary (SAM) axis, hypothalamic-pituitary-adrenal (HPA) axis and the immune system resulting in deleterious effects on health, performance and well-being. What remains unclear, however, is why some individuals are more susceptible to the effects of stress than others. In order to assess the mechanisms by which stress can lead to dysregulation of these systems, and elucidate factors that may serve to predispose or buffer against their effects, it is, unfortunately, necessary to observe individuals during periods of stress. This is typically achieved in two ways; i) to assess individuals who are experiencing naturally occurring periods of stress (e.g., through their work or home life) or ii) to observe individuals during a controlled period of stress usually administered in the lab. Whilst the former method has high external validity, such methods are often time consuming and lack control. In contrast, controlled or lab methods afford more control and greater manipulation of variables, however, such methods often do not stimulate responses in all of the core physiological systems and lack external validity. I will present data concerning the development and application of two novel acute stressors (Multi-tasking Stress and the CO2 Stress Test) which address these issues and when used in combination with appropriate naturally occurring stressors provide a comprehensive measure of an individual’s responses to stress.