Regulation of the proteome by post-translational modifications (PTM) emerges as a major contributing factor to the functional diversity in biology regulating cellular processes. Because PTM are key to the physiologic functions of the proteins involved, it is imperative that we understand the << coding >> that these modifications impart to regulate diverse activities. As estrogen signalling mediates a plethora of PTM not only on the receptors themselves but also on their coregulators, we investigate to << crack >> the ER code. Besides the long-known phosphorylation, other covalent additions such as acetylation, ubiquitination, sumoylation and methylation have been described for estrogen receptors in recent years. These modifications affect receptor stability and activity, and provide potential mechanisms for cell- or-gene-specific regulation. A better understanding of the impact of these PTMs on estrogen receptor should help in the identification of new drugs for breast cancer treatments.