- Although it is well known that physical activity prevents and ameliorates a large number of conditions and chronic diseases, it is also incontrovertible that physical inactivity is becoming more prevalent. This paradox has led some to suggest that genetic/biological factors influence activity levels as opposed to the classical notion that voluntary activity is solely regulated by environmental factors. There is a plethora of recent data showing that there is considerable genetic influence on activity levels in both humans and animals and emerging evidence suggesting potential genomic locations for those genetic factors. Several independent lines of evidence suggest that dopamine receptor 1 (Drd1) and nescient helix loop helix (Nhlh2) are excellent candidate genes for the regulation of physical activity, with several other potential candidate genes only partially supported. This foundation provides the basis for continuing work to identify additional candidate genes, to identify other genetic factors that are involved in the regulation of physical activity, and to investigate the mechanisms by which these genes and genetic factors regulate activity.