This position statement will address in an evidence-based approach some of the important issues and controversies of current drug treatment of depression such as the efficacy of antidepressants, their effect on suicidality and their place in a complex psychiatric treatment strategy including psychotherapy. The efficacy of antidepressants is clinically relevant. The highest effect size was demonstrated for severe depression. Based on responder rates and based on double-blind placebo-controlled studies, the number needed to treat (NNT) is 5-7 for acute treatment and four for maintenance treatment. Monotherapy with one drug is often not sufficient and has to be followed by other antidepressants or by comedication/augmentation therapy approaches. Generally, antidepressants reduce suicidality, but under special conditions like young age or personality disorder, they can also increase suicidality. However, under the conditions of good clinical practice, the risk-benefit relationship of treatment with antidepressants can be judged as favourable also in this respect. The capacity of psychiatrists to individualise and optimise treatment decisions in terms of 'the right drug/treatment for the right patient' is still restricted since currently there are no sufficient powerful clinical or biological predictors which could help to achieve this goal. There is hope that in future pharmacogenetics will contribute significantly to a personalised treatment. With regard to plasma concentration, therapeutic drug monitoring (TDM) is a useful tool to optimize plasma levels therapeutic outcome. The ideal that all steps of clinical decision-making can be based on the strict rules of evidence-based medicine is far away from reality. Clinical experience so far still has a great impact.