Individuals who disproportionately attend to negative aspects of a situation (attention bias), or who unduly interpret ambiguity in a negative manner (interpretive bias) report more psychological ill-effects of stress than those with balanced or positively-skewed inclinations. Cognitive Bias Modification (CBM) techniques improve maladaptive biases through implicitly-based association learning, with induced positive biases buffering the future perception of stress. Six experimental studies investigated the next stage of this link to bolster and significantly enhance the clinical potential of CBM; how natural and modified biases influence the biological response to acute stress. Studies 1-3 established reliable protocols associated with using laboratory stress tasks and measuring salivary stress biomarkers. Studies 4-5 investigated links between natural and trained biases on psychological and biological stress responses. Study 6 tested the immediate robustness of CBM training. While psychological and physiological stress responses were initiated, attentional biases were not found to moderate acute biological stress responses. Conversely, interpretive biases were related to the recovery from the acute stress and positive interpretive training led to a faster biological recovery from acute stress in high test-anxious individuals relative to sham training. However, neither bias was found to moderate the psychological response to stress. Further, evidence emerged to caution a more selective use of CBM. Positive interpretive training led to a more negative bias and slower physiological recovery to stress in individuals with low trait anxiety or inherent positive biases. From these results, information processing biases are proposed to have less influence on genuinely stressful events but, instead, govern the extent to which unthreatening situations are perceived as stressful. Consequently, negative biases are hypothesised to cause unnecessary and excessive perceptions of stress, resulting in chronic hyper-activity. Combined CBM-A/I tools are recommended to jointly realign maladaptive biases, enabling an effective, efficient, but transitory physiological response to real stress.