Like all tissues, the skin ages due to the passage of time (chronologic aging). However, skin is also exposed to external insults, such as sunlight. Aging due to chronic sun exposure (photoaging) is characterized clinically by wrinkling, dyspigmentation and other changes. Chronologic and photoaging of skin have been distinguished at the structural, cellular and molecular levels. However, many underlying mechanisms remain a mystery. Recent sequencing of the human genome and development of genome-wide microarray platforms now permit analysis of skin aging at the level of gene expression. Analysis of gene expression differences between young and older sun-protected and sun-exposed skin showed that photoaging produces many similar (but more severe) changes in gene expression versus chronologic aging. However, some changes are unique to one form of aging or the other. Bioinformatics tools also enable an integrated analysis of gene expression themes and pathways, which may provide new insights into the mechanisms of skin aging and possible interventions. © 2009-Journal of Drugs in Dermatology. All Rights Reserved.