The German National Cohort (GNC) is a joint interdisciplinary endeavour of scientists from the Helmholtz Association, universities and other German research institutes. Its aim is to investigate the development of major chronic diseases (cardiovascular diseases, cancer, diabetes, neurodegenerative psychiatric diseases, pulmonary and infectious diseases), the subclinical stages and functional changes. In 18 study centres across Germany, a representative sample of the general population will be drawn to recruit in total 200,000 men and women aged 20-69 years. In addition to interviews and questionnaires, the baseline assessment includes a series of medical examinations and the collection of a diverse range of biomaterials. In 20% of the participants, an intensified assessment programme is foreseen. Also in 40,000 participants, magnetic resonance imaging of the whole body, heart and brain will be performed. After 5 years, a follow-up examination will be performed in all subjects and active follow-up by postal questionnaires is planned every 2-3 years. The GNC will provide an excellent basis for future population-based epidemiology in Germany and results will help identify new and tailored strategies for prevention, prediction and early detection of major diseases.