Diverse molecular choreography of replication Accurate duplication and transmission of genetic information to the next generation requires complex molecular assemblies. Bleichert et al. review replication initiation across the three domains of life, with a focus on origin selection and helicase loading. These processes identify potential origins of replication and prepare them for subsequent bidirectional replication initiation. There are key similarities and multiple differences in replication mechanisms between eukaryotes, prokaryotes, and archaea and many outstanding questions to be answered. Science , this issue p. eaah6317