Whilst the treatment of major depression has benefited from the development of newer classes of antidepressants, a substantial proportion of patients still fail to respond to medication, or to tolerate adverse events. Whilst no clinical indicators can currently reliably predict patient response to treatment, evidence continues to emerge indicating a significant genetic influence. Individual differences in patient response are increasingly seen as being largely determined by genetic factors that impact pharmacokinetic and pharmacodynamic parameters. These factors will be examined, and practical guidance on prescribing antidepressants will be discussed.