Replication in eukaryotes initiates from discrete genomic regions according to a strict, often tissue-specific temporal programme. However, the locations of initiation events within initiation regions vary, show sequence disparity and are affected by interactions with distal elements. Increasing evidence suggests that specification of replication sites and the timing of replication are dynamic processes that are regulated by tissue-specific and developmental cues, and are responsive to epigenetic modifications. Dynamic specification of replication patterns might serve to prevent or resolve possible spatial and/or temporal conflicts between replication, transcription and chromatin assembly, and facilitate subtle or extensive changes of gene expression during differentiation and development.