Introduction1.1. OverviewThis review has three major goals: (1) to summarize conclusions about the efficacy of post-exposure smallpox vaccination against clinical disease presentation from historic epidemiological reports and modern animal studies; (2) to identify data gaps in these studies; and (3) to summarize the clinical features of orthopoxvirus-associated infections in various animal models in order to identify those models that are most useful for post-exposure vaccination studies.