The aim of this secondary analysis was to present cross-national data about HIV/AIDS related knowledge among 13- to 15-year-old school-going adolescents from the Middle East and North Africa. Data from 23673 school-going adolescents from seven countries (Jordan, Lebanon, Libyan Arab Jamahiriya, Morocco, Oman, Tunisia and United Arab Emirates) that undertook the Global School-Based Student Health Survey between 2004 and 2008 were analysed. HIV/AIDS related knowledge varied significantly between countries and gender. Research for this sensitive topic is scarce in this region. In addition, schools could be among the many key players for HIV/AIDS education.