The estrogen receptor (ER) is a ligand inducible transcription factor that regulates a large number of target genes. These targets are particularly relevant in breast cancer, where the sensitivity of the tumor to estrogens determines whether the patients can be treated with endocrine therapy such as tamoxifen. Identifying genomic ER targets is a daunting task. Quantifying expression levels of suspected target genes after estradiol stimulation or, more recently, using expression microarrays to this effect will reveal which genes are regulated by estradiol, however, without discriminating between direct and indirect targets. The identification of the palindromic sequence that defines the estrogen responsive element (ERE) allows for the in silico discovery of putative ER targets in the genome. However the ER can also bind imperfect EREs and half sites, and can bind indirectly via other factors. Chromatin immunoprecipitation (ChIP) can yield all ER genomic target sites. Coupling of ChIP with genome-wide tiling arrays allows for the genome-wide unbiased identification of direct ER target sequences.