The link between psychological stress and aging is intuitive although the underlying mechanisms are not well defined. Evidence suggests that chronic psychological stress stimulates the autonomic nervous system, renin-angiotensin system, and the hypothalamic-pituitary-adrenal axis when the body attempts to resolve perceived threats to homeostasis. Prolonged activation of these pathways can result in chronic immune dysfunction, increased production of reactive oxygen species, and DNA damage, which are known to contribute to the again of skin and other tissues. Despite the lack of conclusive evidence directly linking psychological stress to skin aging, mechanisms by which stress leads to immune dysfunction, oxidative radicals, and ultimately DNA damage via neuronal, endocrine, and immune modulation may present a possible intervention for skin aging. In addition to the wide array of anti-oxidant therapies being developed to combat aging, the topical use of beta-blockers such as timolol, angiotensin receptor blockers such as valsartan, glucocorticoid blockers such as mifepristone, and cholinergic modulators including botulinum toxin, might be potential therapeutic strategies to prevent skin aging. Given the current understanding of these pathways, it would be premature to utilize such modalities for prevention of skin aging at this time, but future research into this type of topical pharmacologic anti-aging intervention may be promising.