Rationale: Epilepsy is the most common serious neurological condition in the world, and an important cause of mortality and disability in developing countries. Because epidemiological and clinical characteristics of epilepsy vary by region, it is important to know the peculiarities of epilepsy in this area of the American continent. Methods: We searched MEDLINE, IMBIOMED, and LILACS (The Latin-American and Caribbean biomedical database) to identify community-based studies reporting on the prevalence and incidence of epilepsy in Latin America. Studies were included if a definition of epilepsy was given, if data were obtained through standardized questionnaires and if raw population numbers were available for data confirmation. Results: Thirty-three studies fulfilled eligibility criteria, 32 reported on prevalence and three on incidence of epilepsy. The median lifetime prevalence in all countries was 17.8 (range 6–43.2) per 1000 people, and the range for incidence was 77.7–190 per 100,000 people per year. There were no differences between rural and urban areas, by gender, age-group (children, adult, all ages), ascertainment method, or year of study. Conclusions: Measuring the global burden of disease in Latin America requires adequate epidemiological information. This systematic review of epidemiological studies identifies higher prevalence and incidence rates of epilepsy in the general population of Latin America than in northern hemisphere countries. The remarkable heterogeneity found between and even within countries, could be explained by several factors, importantly, socioeconomic and methodological aspects.