Many genetic studies have focussed on dopamine receptors and their relationship to neuropsychiatric disease. Schizophrenia, bipolar disorder, and substance abuse have been the most studied, but no conclusive linkage or association has been found. The possible influence of dopamine receptor variants on drug response has not received as much attention. While there is some evidence that polymorphisms and mutations in dopamine receptors can alter functional activity and pharmacological profiles, no conclusive data link these gene variants to drug response or disease. The lack of unequivocal findings may be related, in part, to the subtle changes in receptor pharmacology that these polymorphisms and mutations mediate. These subtle effects may be obscured by the influence of genes controlling drug metabolism and kinetics. Further insight into the pharmacogenetics of dopamine receptors may require not just more studies, but novel approaches to the study of complex genetic traits and diseases.