This chapter details a comparative genetic analysis of several candidate genes associated with acellular cementum, namely ALPL, BMP-2, BMP-7, and ARNTL. More than 40 species of mammals, reptiles, and birds were included in this analysis. For each gene, we investigated the type of selection that best characterized its evolutionary history, identified species in which these genes were recently subject to positive selection, and demonstrated specific behavioral and morphological characteristics that influence the selection pressure on these genes. We found that, overall, ALPL, BMP-2, BMP-7, and ARNTL have been subject to purifying selection in the examined taxa; however, recent positive selection on three of these genes was identified in species that have experienced recent, rapid evolutionary changes in dental anatomy. In addition, we found that several species-specific characteristics, including diet, lifespan, tooth count, and radicularity, significantly predicted lineage-specific selection pressure on these genes. This chapter demonstrates that cementum genes have undergone significant evolutionary changes, and that certain phenotypic characteristics have influenced such changes