We provide a review of dental replacement features in stem clades of mammals and an hypothetical outline for the evolution of replacement frequency, mode, and sequence in early mammalian evolution. The origin of mammals is characterized by a shift from a primitive pattern of multiple, alternating replacements of all postcanines in most cynodonts to a derived pattern of single, sequential replacement of postcanines. The stem mammal Sinoconodon, however, retained some primitive replacement features of cynodonts. The clade of Morganucodon crown mammals is characterized by the typical mammalian diphyodont replacement in which antemolars are replaced by one generation in anteroposterior sequence, but molars are not replaced. The stem clades of crown mammals including multituberculates and eutriconodonts have an anteroposterior sequential and diphyodont replacement of premolars. By contrast, stem taxa of the trechnotherian clade (Zhangheotherium, Dryolestes, and Slaughteria) are characterized by an alternating (p2 → p4 → p3) and diphyodont replacement, a condition that is shared by basal eutherians. The sequential replacements of premolars in most extant placentals (either anteroposteriorly p2 → p3 → p4 as in ungulates and carnivores, or postero-anteriorly p4 → p3 → p2 as in some insectivores) would represent secondarily derived conditions within eutherians. The single replacement of P3/p3 of metatherians is the most derived for all therian mammals.