Abstract Apurinic/apyrimidinic (AP) endonucleases are versatile DNA repair enzymes that possess a variety of nucleolytic activities, including endonuclease activity at AP sites, 3′ phosphodiesterase activity that can remove a variety of ligation-blocking lesions from the 3′ end of DNA, endonuclease activity on oxidative DNA lesions, and 3′ to 5′ exonuclease activity. There are two families of AP endonucleases, named for the bacterial counterparts endonuclease IV (EndoIV) and exonuclease III (ExoIII). While ExoIII family members are present in all kingdoms of life, EndoIV members exist in lower organisms but are curiously absent in plants, mammals and some other vertebrates. Here, we review recent research on these enzymes, focusing primarily on the EndoIV family. We address the role(s) of EndoIV members in DNA repair and discuss recent findings from each model organism in which the enzymes have been studied to date.