Dogs (Canis lupus familiaris) descend from wolves (Canis lupus) sharing the same ecological niche of cooperative hunters, as humans. Initially, humans and wolves were competitors starting interspecific communication in order to avoid risk of injury. The evolutionary continuity of mammalian brains enabled interspecific prosocial contacts between both of them, which reduced stress, and enabled behavioral cultures leading to genetic isolation of those wolves. Dogs are the first domesticated animal living together with humans for about 25,000 years. Domestication means decreased aggression and flight distance toward humans, thus changes in the stress axis are crucial. The hypothesis of Active Social Domestication considers genetic selection as a necessary prediction but not a sufficient explanation of dog domestication. In addition, dog domestication is suggested to be an epigenetic disclosure. Due to changed stress activity, epigenetic mechanisms affect cerebral receptor activity and regulate transposon expressions, thus shaping brain function and behavior. Interspecific prosocial contacts initiated via serotonin release an enzymatic cascade enhancing, epigenetically, the glucocorticoid negative feedback loop. Reduced chronic stress improved social learning capability and inhibitory control. Over time, those wolves could integrate themselves into human social structures, thus becoming dogs. In analogy, human mental skills, such as creating art and culture, might have also improved during the Upper Paleolithic.