Gregory Crawford and colleagues take a useful approach to consider how regulatory elements contribute to gene expression differences and evolution between primate species (PLoS Genet. 8, e1002789, 2012). The authors report the results of genome-wide DNase-seq in primary skin fibroblasts and lymphoblastoid cell lines from humans, chimpanzees and rhesus macaques, comparing DNase I-hypersensitive (DHS) sites that mark regulatory elements. Whereas most DHS sites are conserved, the authors were able to identify species-specific differences. They further identified several hundred DHS sites that were gained or lost in the human and chimpanzee lineages relative to macaques, as well as a set of common DHS regions shared across species. They compared their data to DNase-seq data sets for 27 human cell types in ENCODE and found that most of the human DHS gains were cell type specific, whereas the common DHS sites were found across human cell types. Species-specific DHS sites are enriched near genes showing differential expression in these species. The authors also found evidence for branch-specific selection at DHS sites that were gained in the human or chimpanzee lineages. This work provides insights into the tissue- and species-specific activities of regulatory elements and their role in evolution.