Objective: To synthesize the evidence underpinning the benefits and risks of influenza vaccination for inclusion in communication and outreach campaigns. Background: Influenza A virus is a seasonal contributor to worldwide morbidity and mortality. Children, the immunocompromised, and the elderly are at higher risk of influenza complications. Compliance with vaccination remains below the optimum effectiveness level despite an estimated annual global mortality of 300,000 to 500,000. Methods: Publications describing concerns and objections to the influenza vaccination were reviewed. Based on these reviews, Medical Subject Heading (MeSH) terms were selected to query major databases for relevant information on effectiveness, risks, compliance, and acceptance of seasonal and 2009 pandemic influenza vaccines. A standardized approach to the rating of the evidence was developed. The synthesized evidence on vaccine effectiveness, enacted medical and public health policies, and communication practices was discussed with a group of experts and subjected to an external peer review. Results: Prior surveys identified poor understanding of influenza health risks and lack of access to the vaccine as major objections to immunization. There is good evidence that the seasonal vaccine provides protection against influenza, and vaccine complications are rare. Influenza vaccination rates remain low suggesting that the potential economic and health benefits of the vaccine have not yet been realized. Epidemiological studies quantifying the success of the general public's use of precautionary practices are lacking. Prospective studies on vaccine efficacy were not found in the published literature. Few cross-sectional studies on immunization compliance among healthcare workers (HCWs) and different population groups were found in our literature searches. Well-designed epidemiological studies on the benefits and risks of influenza vaccination programs are available for a limited number of countries and select population groups. Discussion: It is postulated that the success of an immunization program depends on advanced planning and sustained communication campaigns. Evidence-based education on the benefits of vaccination can help improve compliance among HCWs and the public. Interpreting and explaining scientific data end knowledge is complex, and conveying this information to the public should target primarily the benefits and risks of vaccination. Educational campaigns should include well-defined strategies compatible with cultural, behavioral, and social constructs of each community. Conclusions: There is good evidence that seasonal influenza vaccination is a reliable and effective public health tool for reducing the adverse health and economic consequences of this disease. This evidence should be clearly articulated in all influenza educational and outreach campaigns. Evidence supporting the added efficacy of influenza vaccines, together with physical and sanitary measures to interrupt transmission, should be the subject of additional studies. Physical countermeasures should form the basis for a sustained outreach campaign since they also offer protection against other infections. The availability of effective influenza vaccines in the late summer or early fall could help maintain public confidence and improve compliance. Large-scale international epidemiological studies of influenza vaccine acceptance are required to plan successful immunization campaigns. Applicability: Clear, concise and understandable evidence-based information, coupled with sustained education campaigns, is critical for promoting vaccination. Immunization campaigns should involve the participation and support of all HCWs to promote public confidence, minimize confusion and improve compliance. After the events of September 11, 2001, and the mailing of anthrax-laced letters, all U.S. critical infrastructure personnel and vulnerable individuals should receive the seasonal influenza vaccine for biodefense purposes. The use of the influenza vaccine can help differentiate a bioterrorist incident involving pulmonary anthrax from seasonal and pandemic influenza. Study Limitations: This study used published information on the benefits and risks of vaccination in select population groups: the elderly, residents in long-term care facilities, and patients with chronic afflictions who were already under medical care before receiving the vaccination. Proper caution should be exercised when extrapolating these findings to other demographic groups or a healthy population in the absence of specific epidemiological data. Ethical, societal and religious concerns, beliefs and controversies surrounding influenza immunization policies were not addressed.