Modern vaccines may be very costly, and society needs to consider vaccination against other preventive and curative interventions. An economic assessment of health care programmes implies to quantify costs and assess health consequences in order to set better priorities. The main challenge lies in obtaining valid estimates of health effects and side effects and the consequences of herd immunity and serotype shift. This article discusses the methods and challenges of economic evaluation of vaccination programs, with vaccination against whooping cough and pneumococcal disease as examples.