Personalized drug therapy proffered by pharmacogenomics must be based on the recognition of inherent genetic individuality, rather than relying on inter-ethnic differences in the frequency of polymorphisms that affect the pharmacokinetics and targets of drugs. This is particularly significant in admixed populations, in which the substructure created by inter-ethnic crosses further increases the fluidity of racial and/or ethnic labels. Inter-ethnic admixture is either common or increasing quickly in many, if not most, populations, and so extrapolation on a global scale of pharmacogenomic data from well-defined ethnic groups is plagued with uncertainty. To impact positively on global health, pharmacogenomics must broaden its scope of investigation with respect to both target and population diversity, and avoid the risk of contributing to the creation of a genomics divide between regions and nations. In this review, I examine the challenges and advantages of studying pharmacogenomics in admixed populations, drawing examples mainly from the trihybrid populations of the Americas.