Populations evolve as mutations arise in individual organisms and, through hereditary transmission, gradually become ''fixed'' (shared by all individuals) in the population. Many mutations have essentially no effect on organismal fitness and can become fixed only by the stochastic process of neutral drift. However, some mutations produce a selective advantage that boosts their chances of reaching fixation. Genes in which new mutations tend to be beneficial, rather than neutral or deleterious, tend to evolve rapidly and are said to be under positive selection. Genes involved in immunity and defense are a well-known example; rapid evolution in these genes presumably occurs because new mutations help organisms to prevail in evolutionary ''arms races'' with pathogens. Many mammalian genes show evidence of positive selection, but open questions remain about the overall impact of positive selection in mammals. For example, which key differences between species can be attributed to positive selection? How have patterns of selection changed across the mammalian phylogeny? What are the effects of population size and gene expression patterns on positive selection? Here we attempt to shed light on these and other questions in a comprehensive study of ,16,500 genes in six mammalian genomes.