Once a new vaccine has been approved, public health expertise is required to support the decision regarding its potential inclusion in the national immunization schedule. This analysis, based on an assessment of the risk-benefit balance and the cost-effectiveness ratio, is a multidisciplinary process. While it relies heavily on epidemiological and immunological expertise, it also requires biostatistical and economic input if the long-term consequences of vaccination are to be taken into account. Indeed, the main factors driving the decision are the burden of the disease, the vaccine’s characteristics in terms of effectiveness and safety, the cost of vaccination, the feasibility of adding the vaccine to the schedule, the public demand for this vaccination, and the positive or negative indirect effects of widespread vaccination on the epidemiology of the disease, in addition to the direct protective effect for vaccinated individuals. New vaccines generally have a more limited epidemiological impact than older vaccines, in a context of growing societal demands regarding the safety of drugs, and especially vaccines. Both the actual and perceived benefit-risk ratios for newer vaccines appear questionable. The possibility of adverse epidemiological consequences resulting from either insufficient vaccination coverage or serotype (or serogroup) replacement is another factor that makes decisions regarding vaccination strategies increasingly complex.