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While a significant number of studies have been undertaken to increase knowledge regarding social, cultural, and economic factors associated with utilization of vaccines, fewer studies have examined participation in vaccine trials and feasibility studies. The experimental nature of trials adds a layer to the already complex contexts of public health vaccination programs. For over ten years, we have been involved in the development and implementation of socio-cultural research in Asia and Africa utilizing a range of qualitative and quantitative methods toward assessment of community, scientific, and policy perceptions and knowledge in relation to vaccine trials and feasibility studies. In this paper, we present a framework for assessing the multiple perspectives of local, national, and international stakeholders and anthropology's contribution to research for the development of communication campaigns and social mobilization before, during, and after trials and feasibility studies.