Tardive dyskinesia (TD) affects about one fifth of schizophrenia patients following chronic exposure to dopamine receptor antagonist drugs. Drug- and patient-related risk factors for the development of TD have received much research attention but appear to predict only a minor part of the variance in the incidence of TD. This chapter reviews this rapidly developing field, incorporating recently available molecular genetic tools for a renewed exploration of the biological basis of TD. Genes coding for known drug targets can be directly explored for involvement in TD susceptibility. Genetic variability in dopamine receptors may predict functional differences in response patterns to neuroleptic agents and may be relevant to the expression of idiosyncratic reactions. Other promising findings, including the reported associations with 5-HT2A receptor (5-HTR2A) and 5-HTR2C and manganese superoxide dismutase (MnSOD) genetic polymorphic sites, require independent replications.