Although it is now widely recognized that tobacco smoke has negative effects on the skin, the molecular mechanisms underlying its skin-aging effects remain uncertain. Epidemiological studies indicate that tobacco smoking is a strong independent predictor of facial wrinkle formation and other aspects of premature skin aging. Recent in vivo studies in humans and mice provided the first direct evidence that tobacco smoke causes premature skin aging, and they have begun to reveal the molecular changes in the skin that occur in response to it. Water-soluble tobacco smoke extract, which predominantly produces oxidative stress when applied topically to cultured skin fibroblasts, impairs collagen biosynthesis. Matrix metalloproteinases, which degrade collagen, are induced dose-dependently by tobacco smoke extract as well as by other constituents that trigger the aryl hydrocarbon receptor (AhR), a ligand-dependent transcription factor that mediates the toxicity of several environmental contaminants, including photoproducts in the body generated by UVB radiation. Tobacco smoke also contains many non-water-soluble constituents that activate the AhR pathway. Our most recent studies using hexane-soluble tobacco extract indicate that activation of the AhR pathway may play a role in the premature skin-aging effects of tobacco smoke exposure.Journal of Investigative Dermatology Symposium Proceedings (2009) 14, 53-55; doi:10.1038/jidsymp.2009.13.