Abstract : Although interest in the rate of molecular evolution and the molecular clock remains high, our knowledge for most groups in these areas is derived largely from a patchwork of studies limited in both their taxon coverage and the number of genes examined. Using a comprehensive molecular data set of 44 genes (18 nDNA, 11 tRNA and 15 additional mtDNA genes) together with a virtually complete and dated phylogeny of extant mammals, I 1) describe differences in the rate of molecular evolution (i.e. substitution rate) within this group in an explicit phylogenetic and quantitative framework and 2) present the fi rst attempt to localize the phylogenetic positions of any rate shifts. Significant rate differences were few and confirmed several long-held trends, including a progressive rate slowdown within hominids and a reduced substitution rate within Cetacea. However, many new patterns were also uncovered, including the mammalian orders being characterized generally by basal rate slowdowns. A link between substitution rate and the size of a clade (which derives from its net speciation rate) is also suggested, with the species-poor major clades (“orders”) showing more decreased rates that often extend throughout the entire clade. Significant rate increases were rare, with the rates within (murid) rodents being fast, but not significantly so with respect to other mammals as a whole. Despite clear lineage-specific differences, rates generally change gradually along these lineages, supporting the potential existence of a local molecular clock in mammals. Together, these results will lay the foundation for a broad-scale analysis to establish the correlates and causes of the rate of molecular evolution in mammals.