The Vaccines and Medications in Pregnancy Surveillance System (VAMPSS) has been designed to assess systematically the safety of vaccines and medications during pregnancy and is suited ideally to evaluate the gestational safety of seasonal and pandemic influenza vaccine and influenza antivirals. VAMPSS is coordinated by the American Academy of Allergy Asthma and Immunology and includes 2 complimentary data collection arms (prospective cohort and case-control surveillance) and a standing independent advisory committee. Both data collection arms obtain information directly from the mother, which facilitates accurate capture of exposures and potential confounders. The full range of perinatal outcomes, which includes specific birth defects, is assessed. Information that is obtained from VAMPSS should allow enhanced prevention and improved treatment of influenza during pregnancy by the identification of any exposures that might be associated with important risks and the provision of reassurance for exposures that are found to be relatively safe.