2016 by John Wiley & Sons, Inc. All rights reserved. Vaccination is an important method for disease control and prevention for horses. This chapter first presents summary tables of the AAEP guidelines for foals and broodmares, and then explains the difference between vaccine efficacy and vaccine effectiveness. In a cohort study, vaccinates (exposed cohort) and non-vaccinates (unexposed cohorts) would be followed forward in time after vaccination, and evaluated for development of disease and other outcomes of interest. If the vaccine is effective against the disease of interest, the incidence of disease will be lower among vaccinates than among unvaccinated horses. The safety of vaccines may be perceived differently than other medical interventions, because vaccines are administered primarily to healthy individuals. Vaccination protocols vary even for horses residing within the same barn. A middle-aged gelding retired from competition that has limited exposure to other horses has a different risk level than a young filly actively engaged in showing.