Baculoviruses are a family of arthropod-specific viruses that mainly affect insects of the orders Lepidoptera, Hymenoptera, and Diptera. In nature, baculoviruses establish infection in their hosts orally and a battery of proteins designated as per os infectivity factors play pivotal roles in baculovirus per os infection. This review summarizes the basic characteristics of baculovirus and discusses the main events that baculovirus establishes per os infection, including the evolutionary advantages for baculovirus to initiate infection through the oral route, the binding and fusion of baculovirus virions with insect midgut microvilli and the functional roles of baculovirus per os infectivity factors. These achievements and advances should promise to shed light on the understanding and utilization of baculovirus for bio-control and exogenous gene expression in the future.