This review will provide an overview of literature that has linked caregiver stress with development and progression of disease, via interactions between the hypothalamic–pituitary–adrenal (HPA) axis and immune systems. The link between caregiver stress and dysregulation of key physiologic mediators has, in the main, focussed on elderly caregivers of spouses with degenerative illness, i.e., dementia. In these populations, aberrations of both endocrinological and immunologic mediators have been demonstrated. However, as a function of their advancing age, elderly populations experience natural dysregulation of the HPA axis and decline of immunologic efficacy. More recently, research has begun to assess whether caregiver stress exacts a similar physiologic toll on non elderly caregivers, i.e., parents of medically fragile children. Dysregulation of endocrinological and immunologic mediators have been observed in both populations, however, more consistently so in the elderly. The authors suggest that, by considering specific characteristics of the care recipient, i.e., type of impairment, and concomitant changes in the caregiving experience, i.e., caregiving intensity, as well as the role of dyadic support, researchers might be better poised to explain discrepant physiologic findings between elderly and non elderly caregivers and reconcile similar physiologic inconsistencies between different, non elderly populations.