Genetic variation of SLC6A4, HTR1A, MAOA, COMT and BDNF has been associated with depression, variable antidepressant drug responses as well as impacts on brain regions of emotion processing that are modulated by antidepressants. Pharmacogenetic studies are using psychometric outcome measures of drug response and are hampered by small effect sizes that might be overcome by the use of intermediate endophenotypes of drug response, which are suggested by imaging studies. Such an approach will not only tighten the relationship between genes and drug response, but also yield new insights into the neurobiology of depression and individual drug responses. This article provides a comprehensive overview of pharmacogenetic, imaging genetics and drug response studies, utilizing imaging techniques within the context of antidepressive drug therapy.