Monoubiquitination of histone H2B has emerged as an important chromatin modification with roles not only in transcription but also in cell differentiation, DNA repair or mRNA processing. Recently, the genome-wide distribution of histone H2B ubiquitination in dif-ferent organisms has been reported. In this review we discuss the mechanisms regulating H2B ubiquitination and its downstream effectors as well as the suggested functions for this mark in light of these recent studies.