In all organisms, successful cell division requires accurate copying of chromosomal DNA. To duplicate their genomes, all cells use a multiprotein apparatus known as the replisome (reviewed by Benkovic et al., 2001; McHenry, 2003; Yao and O’Donnell, 2009). The fundamental components of the replisome are conserved across viruses, bacteria, archaea, and eukaryotes (Table). They include a helicase to unwind the double-stranded DNA, a polymerase(s) to synthesize new strands of DNA, and a clamp loader to organize the complex on the DNA. The replisome assemblies at a region of the DNA, called the replication fork, where the double-stranded DNA is separated into two individual strands, which are both subsequently copied in the 5′ to 3′ direction of the DNA. In this SnapShot, we compare the specific components of the replisome in Escherichia coli with those of the replisome in eukaryotes. In addition, we describe how the lagging strand is synthesized from Okazaki fragments. Table