The Depression Initiative is a nationwide programme led by the Trimbos Institute in which 30 mental health organisations, 80 general practices, the VU University Medical Centre, the EMGO Institute and the Institute for Medical Technology Assessment (iMTA) collaborate to achieve the following objectives: national implementation of the multidisciplinary guidelines for depression; evaluation of the cost-effectiveness of this approach in primary care, industrial medicine and hospital settings; and outcomes management systems aimed at informing patients, practitioners and health insurers about the most effective ways to tackle depression. Within the Trimbos Diagnostics and Treatment (D&T) Programme, five cost-effectiveness studies are being conducted in relation to the Depression Initiative.