The presence of a placenta is an important synapomorphy that defines the mammal clade. From the fossil record we know that the first placental mammal lived approximately 125 million years ago, with the chorioallantoic placenta evolving not long after. In this thesis a set of 22 complete genomes from Eutherian, non-Eutherian and outgroup species are compared, the aim being to identify protein-coding and regulatory alterations that are likely to be implicated in the emergence of mammal placenta in the fossil record. To this end we have examined the roles played by positive selection and miRNA regulation in the evolution of the placenta. We have identified those genes that underwent functional shift uniquely in the ancestral placental mammal lineage and that are also heavily implicated in disorders of the placenta. Carrying out a thorough analysis of non-coding regions of the 22 genomes included in the study we identified a cohort of miRNAs that exist only in placental mammals. Many of the placenta related genes described above have multiple predicted “placenta-specific” miRNA binding sites. Together these results indicate a role for both adaptation in protein-coding regions and emergence of novel noncoding regulators in the origin and evolution of mammal placentation.