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Drug response is affected by genetic and non-genetic factors, such as dietary compounds, sex, disease status and multiple drug therapy. Inherited determinants of drug disposition remain, however, the major cause of inter-individual differences due to pharmacogenetic polymorphism in drug metabolizing enzymes and transporters, or drug targets. Differences on ethnicity may have a profound impact on drug clearance, affecting the safety, efficacy and dosing regimen. In the context of tropical regions, the situation may be even more serious due to endemic infectious diseases and multiple drug therapy, which may affect drug clearance. In this review, we focus on the pharmacogenetics of the Cytochrome P450 superfamily, responsible for the highest contribution for variability among drug metabolizing enzymes, among ethnic groups from tropical settings.