Senecavirus A (SVA) is an emerging picornavirus that causes vesicular disease (VD) in swine. SVA was first detected as a cell culture contaminant in 2002; however, it wasn’t until 2015 that SVA was determined to be an etiologic agent of VD in pigs. Retrospective analysis suggests SVA has circulated in swine in the United States (USA) since as early as 1988. Although SVA-associated VD is self-limiting, the occurrence of vesicular disease in swine is highly disruptive to production as in many countries extensive testing to rule out foreign animal diseases (FADs), such as foot-and-mouth disease (FMD) and swine vesicular disease (SVD), is required. Additionally, SVA has been reported to have potentially fatal outcomes for neonatal piglets. Adult animals infected with SVA often exhibit lethargy prior to the development of vesicular lesions on the snout, lips, tongue, coronary band, and/or hooves. Lesions typically heal within 2 weeks. Definitive diagnosis requires real-time RT-PCR testing and differential diagnosis from other VD-causing agents. Notably, SVA has been shown to establish persistent infection in the tonsil of infected swine, with intermittent virus shedding detected for up to 3 months post clinical disease in the absence of clinical signs. Currently there are no licensed vaccines or anti-viral therapies for SVA. In the present review we summarize the current knowledge about SVA infection biology, epidemiology, and pathogenesis.