The replication of the genome during S phase is a crucial period for the establishment and maintenance of programmes of differential gene activity. Existing chromosomal structures are disrupted during replication and reassembled on both daughter chromatids. The capacity to reassemble a particular chromatin structure with defined functional properties reflects the commitment of a cell type to a particular state of determination. The core and linker histones and their modifications, enzymes that modify the histones, DNA methylation and proteins that recognize methylated DNA within chromatin may all play independent or interrelated roles in defining the functional properties of chromatin. Pre-existing protein-DNA interactions and DNA methylation in a parental chromosome will influence the structure and function of daughter chromosomes generating an epigenetic imprint. In this chapter we consider the events occurring at the eukaryotic replication fork, their consequences for pre-existing chromosomal structures and how an epigenetic imprint might be maintained.