The objective of this study was to systematically review research that has focused on knowledge of and attitudes towards epilepsy among teachers. Embase, PubMed, PsycINFO, Google Scholar, and Cochrane library databases from 2000 to 2017 were searched. Cross-sectional and interventional studies were included and analyzed for quality. Thematic analysis was used to identify common themes in the results. Fifty-four eligible studies (17,256 total participants in 27 different countries) were identified in the search period including seven studies that focused on assessing attitudes and knowledge before and after an educational intervention. It was not possible to systematically analyze levels of knowledge and nature of attitudes because of the wide variety of mostly bespoke study specific instruments used. Few studies employed valid and reliable instruments. Thematic analysis revealed three main themes in the results: 1.) deficits in knowledge and negative attitudes were pervasive across all studies; 2.) teachers often had a negative attitude towards participation of children with epilepsy in physical activities/sport; and 3.) teachers often expressed limited knowledge of seizure management/emergency procedures. There was a lower level of knowledge and more negative attitudes among teachers towards epilepsy compared with other conditions. All studies focusing on interventions showed that at least some aspects of knowledge and attitudes improved as a result of teacher participation in an educational intervention, but study quality was universally rated as low. A higher level of education and experience of teaching a child with epilepsy was significantly associated with greater knowledge in a number of studies. Additionally, having experience of teaching a child with epilepsy and greater assessed knowledge of epilepsy were associated with more positive attitudes. The wide range of methods used makes it difficult to generalize regarding level of attitudes and knowledge among teachers towards epilepsy. Nevertheless, all studies indicate that there are some deficits in knowledge of and negative attitudes towards epilepsy among teachers. It would appear that knowledge and attitudes can be improved by educational interventions. Future research should focus on developing psychometrically sound assessment instruments that can be used globally and on identifying the most effective ways of delivering efficacious educational initiatives employing robust study designs.