Introduction1.1. OverviewThis review has three major goals: (1) to summarize conclu-sions about the efficacy of post-exposure smallpox vaccinationagainst clinical disease presentation from historic epidemiologi-cal reports and modern animal studies; (2) to identify data gapsin these studies; and (3) to summarize the clinical features oforthopoxvirus-associated infections in various animal models inorder to identify those models that are most useful for post-exposure vaccination studies.