Unipolar depressive disorders are among the most frequent reasons for utilizing the health care system. Although efficacious treatments are available and further advances have recently been made there is still a need for improving diagnostic and therapeutic procedures. Alignment of treatment on evidence-based treatment guidelines establishes an essential mainstay. The new S3 and National Health Care guidelines on unipolar depression, the compilation of which was coordinated by the German Society of Psychiatry, Psychotherapy and Neurology (DGPPN) and which were approved by 29 scientific and professional associations, is the ambitious effort to present state of the art evidence and clinical consensus for the treatment of depression. For pharmacotherapy of depression differentiated recommendations can be given, also separate from and in addition to psychotherapy.