Informed consent is universally recognized as a central component of ethical conduct in scientific research. Investigators working with diverse populations throughout the world face myriad challenges. The application of standards for informed consent can be daunting for researchers when they face the pragmatic constraints of the field and the reality of cultural beliefs about consent that may be in direct conflict with regulatory requirements. This paper explores cultural and social factors underlying informed consent for health research with diverse populations in international settings. Sociocultural influences on comprehension of information, perceptions of risk, and beliefs regarding decisional authority are reviewed. The implications of power inequities between study sponsors, researchers and participants are also considered. Issues associated with the development and preparation of consent forms, including translation and documentation are highlighted. Recommendations for good practices are outlined and future directions for research are explored.