The ubiquitin system is involved in numerous cellular processes, regulating the amounts and/or activities of specific proteins through posttranslational coupling with ubiquitin or ubiquitin-like proteins. In spermatogenesis, there appears to be a special requirement for certain components of the ubiquitin system, as exemplified in human and mouse by mutation of USP9Y and HR6B, respectively. Both genes encode proteins which take part in the ubiquitin system and are ubiquitously expressed, but their mutation generates no apparent phenotype other than male infertility. Different phases of mammalian spermatogenesis probably require different specialized activities of the ubiquitin system. It is anticipated that ubiquitination activities similar to those required during mitotic cell cycle regulation will play some role in control of the meiotic divisions. In spermatocytes, there is an intricate link among DNA repair, the ubiquitin system, and regulation of meiotic chromatin structure, as indicated by the co-localization of proteins involved in these processes on meiotic recombination complexes. HR6B and its nearly identical homolog HR6A are multiple function proteins, with ubiquitin-conjugating activity and essential roles in post-replication DNA repair. HR6B, possibly together with the ubiquitin-ligating enzyme mRAD1 8Sc, is most likely involved in chromatin re-organization during the meiotic and post-meiotic phases of spermatogenesis. Biochemical data indicate that, in particular during spermiogenesis, the general activity of the ubiquitin system is high, which most likely is related to the high requirement for massive breakdown of cytoplasmatic and nuclear proteins during this last phase of spermatogenesis.