The review demonstrates that structural comparison of DNA polymerase architecture suggests a nucleotide gateway to the polymerase active site. The identity, crystallographic structures, accessory domains, and biological function of the polymerases have been analyzed. Investigations reveal that the polymerase domain of most DNA polymerases is comprised of three subdomains. The architectural arrangement of the subdomains of A-, B-, and Y-family DNA polymerases has been compared to a right hand and is referred to as fingers, palm, and thumb. The palm subdomains are homologous despite the structures of the fingers and thumb subdomains being distinct among these families. The active site acidic residues that coordinate two divalent metals necessary for nucleotidyl transfer are found in the palm subdomain.