This chapter considers different vaccination strategies and important concepts for monitoring vaccine performance in the field, including vaccine coverage, herd immunity, and vaccine effectiveness studies. Where infectious agents are endemic, with a high risk of exposure to infection, vaccination may be used to protect individual groups or animals from disease on a risk basis. The process of vaccination involves multiple decisions and activities. Problems can arise due to poor strategy, inadequate implementation, or changes in the pathogen or the livestock industry. The advantages of vaccine efficacy studies include rigorous controls for biases by sex/age, etc., as study individuals are randomly allocated into groups. Furthermore, they require recording of vaccination status and include a prospective, active monitoring phase for AR, including laboratory confirmation of the infectious status/outcome of interest and vaccine immunogenicity. Measuring vaccination coverage and postvaccination immunity are two key indicators establishing that vaccination has been applied correctly.