The two LTR retrotransposon-derived genes PEG10 and PEG11/RTL1 play essential roles in placental formation and its maintenance in the current mammalian developmental system. The former is a therian-specific and the latter is a eutherian-specific gene, suggesting that once they had been acquired in common ancestors of the therian and eutherian mammals, respectively, they have underwent positive selection during the course of mammalian evolution due to developmental advantages they conferred. Thus, their exaptation had a profound impact on the evolution of mammalian viviparity as well as the emergence of the therians and eutherians, the infraclass and subclass of mammals, respectively. How the exaptation of PEG10 and PEG11/RTL1 come to take place in the mammalian lineage? We propose that the exaptaion mechanism comprises two subsequent steps. The first follows the pattern of nearly neutral theory of molecular evolution, where the retrotransposons were neutralized by DNA methylation and genetic drift fixed them in the population. At the next step, Darwinian evolution propagated these genes into all the therian and eutherian population by natural selection. In the course of these processes, the placenta, a mammalian-specific extraembyonic tissue, may have been of special importance as a sort of “natural laboratory” for mammalian evolution.