HIV and AIDS is recognised as not only a global public health problem, but also as a problem that is  embedded in and influenced by cultural, social and economic factors. Conventional public health preventive interventions and awareness campaigns, focusing on improved knowledge and individual behavior change, have largely failed to reduce the transmission of HIV. This observation has required national and international health authorities as well as NGO´s in particularly affected areas, such as South Africa, to revisit how they communicate relevant, consistent and correct information about HIV and AIDS. Due to this global crisis, practitioners and theorists need to rethink about the creative application of communication strategies. Communication serves as a means to discuss health problems, and specific determinants of health with a final goal of “translation of science into practice” (Parvanta, 2011:84). One of the most promising communication approaches to address HIV and AIDS, and in South Africa more specifically, has been Entertainment Education (EE), a creative and engaging communication strategy used to bring about behavioural and social change mainly addressing development and health issues. EE, as a strategy, acknowledges that HIV and AIDS interventions must integrate both cultural and structural (social change) concerns. Yet, ambiguity surrounding how to design and implement culturally appropriate projects has made it more difficult to develop programmes in this manner. This study revisits perceptions of EE from a global audience perspective, using a South African developed EE television series, Intersexions, as a case study. The overall objective of the study is to explore what these perceptions can tell us about the application of EE in various countries and socio-economic and cultural contexts. Young people from Universities in Malaysia, South Africa, United Kingdom, United States, , the Netherlands and Sweden, between the age of 18-25 participated in focus group discussions after the screening of two episodes of Intersexions. The data collected from various countries offers empirical motives, using a mixed methods approach to revisit how we define EE, and how EE in practice can inform further theoretical developments in the field. The research employs an interpretivist approach and takes the form of a reception analysis of participant responses to the Intersexions episodes, and particularly from the media-culturalist perspective and media-materialist approach.