Diverse histone modifications, such as acetylation, methylation and ubiquitylation have been linked to the regulation of cellular activities such as transcription, repair and replication. The mechanisms by which histone modifications contribute to the transcription process are not fully understood; however increasing evidence suggests that they work together in the form of a histone code to regulate the recruitment of chromatin-modulating factors [1-3]. Histone ubiquitylation has been found to be an important chromatin modification with roles in trans-histone modification and transcriptional regulation. In the past several years, there has been dramatic progress in the identification of factors that control ubiquitin attachment to the histone. Recent advances concerning core histone H2A ubiquitylation and transcriptional regulation will be reviewed and the cellular functions of these histone modifications will be discussed.