This thesis aimed to increase understanding of the underlying physiological sources of the substantial inter-individual variability in heart rate (HR) and blood pressure (BP) reactions to acute psychological stress. This aim was achieved using a multi-method approach that included meta-analysis, laboratory studies, and prospective secondary analysis of epidemiological data. Chapter 2 implicated beta-adrenergic sympathetic activation and parasympathetic withdrawal in the cardiovascular stress response and showed that autonomic changes vary as a function of stress task, age, and sex. Chapter 3 demonstrated that individual differences in a unique HR complexity marker accounted for a significant amount of the observed variance in HR reactivity and that this effect was independent of task performance and changes in autonomic activity and respiration. Chapter 4 revealed that individual differences in resting physiological allostatic load related to HR reactivity such that higher allostatic load indicated lower reactivity. Finally, in Chapter 5, multivariate cluster analysis of HR, systolic and diastolic BP reactivity resolved a large sample into four homogenous clusters, each displaying significantly different reactivity patterns and risk of hypertension at 5-year follow-up. The research reported in this thesis confirms already suspected physiological sources of individual difference but also reveals novel sources that deserve further inquiry.