Proliferating cells need to synthesize large amounts of histones to rapidly package nascent DNA into nucleosomes. This is a challenging task for cells because changes in rates of DNA synthesis lead to an accumulation of excess histones, which interfere with many aspects of DNA metabolism. In addition, cells need to ensure that histone variants are incorporated at the correct chromosomal location. Recent discoveries have highlighted the importance of regulated histone proteolysis in preventing both the accumulation of excess histones and the mis-incorporation of histone variants at inappropriate loci.