Since their discovery in the early nineties, the human arylamine N-acetyltrasferase (NAT) genes have been the subject of a tremendous number of molecular anthropological studies describing their nucleotide diversity in a wide range of populations worldwide. While (HUMAN)NAT2 presents a high number of nucleotide substitutions, with seven of them reaching polymorphic frequencies in almost all human populations, and a high level of non-synonymous changes relative to synonymous, (HUMAN)NAT1 is much less diverse, particularly in its coding region. A pseudo-gene, NATP, the third member of this small gene family, harbors a diversity similar to NAT2. In accordance with that, selective neutrality tests suggest that (HUMAN)NAT1 and (HUMAN)NAT2 evolve under distinct selective regimes. An evolution of (HUMAN)NAT2 under positive population-specific pressures is proposed to be probably linked to the mode of subsistence and/or the chemical environment populations live in, as reflected by climatic zones and biomes; in contrast, for (HUMAN)NAT1, functional constraints determining the strength of purifying selection are generally invoked.