Depression is a significant problem in the elderly population and is often accompanied by cognitive changes and agitation. Hypothalamic-pituitary axis dysfunction may occur in some depressed elderly patients and represent a non-specific physiological hyperarousal state. Moreover, recent evidence confirms that antidepressants down-regulate beta-adrenergic receptors in the central nervous system. These findings provide the background for proposing that depression may result from an age-specific, stress-induced dysfunction of the beta-adrenergic receptor system in a subgroup of the geriatric population. A bio-psycho-social model for understanding and developing innovative treatment strategies for depression in the elderly is presented.