Agricultural biotechnology has the potential to help address a wide range of public health, nutritional, agricultural, and environmental problems in developed and developing countries, as described in a wide variety of scientific (NRC 1985), government (Glickman 1999), industry (Council for Biotechnology Information n.d.), and international (Persley and Lantin 2000; FAO 2003) sources. Despite this potential, the commercialization of the first generation of crops based on these technologies has met with concern and protests from consumer and public interest groups (Consumer's Union n.d.), environmental groups (NRDC 2000), and some governments (EC 2000) and scientists (Union of Concerned Scientists n.d.). This conflict has grown to such proportions that it has resulted in the banning or slowing of the commercialization or use of these products in some countries (Economist 1999), disrupted the distribution of food aid in drought-stricken southern Africa (Economist 2002), reduced U.S. exports of major commodities (Economist 2000), affected the value of Wall Street stocks for major agricultural biotechnology companies (Financial Times 2000), and become a major issue of contention in the regulation of international trade (Financial Times 2003). Many of the proponents of agricultural biotechnology have suggested that the issue should be resolved through the application of sound science (Prakash and Bruhn 2000) and that it would be unethical to ban the use of or inhibit the potential benefits associated with this technology for addressing serious problems related to public health, nutrition, poverty, and the environment (Leisinger 2000; Pinstrup-Andersen and Schioler 2000). Many of the critics have called into question the adequacy of the scientific knowledge (Wolfenbarger and Phifer 2000; Clark and Lehman 2001) about this technology, questioned its benefits and raised concerns regarding its potential risks (PSRAST 1998), and claimed that regulatory decisions have been based more on politics than on science (Eichenwald, Kolata, and Petersen 2001; Ferrara 2001). In contrast to the first generation of genetically modified (GM) crops, which have been designed to address production problems, the second-generation crops currently under development will include a much wider range of alterations. One set will involve changes of potential interest to consumers in developed and developing countries, such as changes in the levels and types of specific fatty acids, vitamins, minerals, phytochemicals, and antinutrients (e.g., phytate). A second set of genetic modifications will focus on agronomic, environmental, and nutritional traits relevant specifically in developing countries, such as drought and saline resistance, insect protection, antiviral and antifungal properties, and enhanced iron, zinc, folate, or pro?vitamin A content, among others. In general, the genetic, metabolic, and food compositional changes in these future crops are expected to be more complex than those of the first-generation crops and may pose more complex regulatory questions (FDA 2001; Kuiper et al. 2001). The purpose of this chapter is to describe the food safety and consumer issues raised by GM foods, with a particular focus on the choices and trade-offs relevant to southern Africa. Although the ultimate focus of the chapter is on the choices and policy trade-offs relevant to southern Africa, it begins with a detailed analysis of how GM foods are regulated in the United States by the Food and Drug Administration (FDA). This is because FDA policies remain the authoritative position of the U.S. government as applied to the United States and, to a large extent, as projected into international and bilateral discussions and negotiations. Therefore, it is important that developing countries become very knowledgeable concerning FDA policies and their scientific, legal, and political bases so that they can engage in those discussions and negotiations on a more equal footing. In addition, an examination of how the scientific, legal, and political considerations were addressed in the U.S. context holds lessons for southern African countries as they ponder the most appropriate institutional and procedural mechanisms for them to use to reach judgments and develop policies of their own. The second section of this chapter builds on the first by placing the scientific considerations in the southern African context. This section highlights the significant differences between the U.S. and southern African contexts, the even greater scientific uncertainties in the southern African context as compared to the U.S. context, and the implications for research and policy development. The third and final section provides a framework for discussing policy options and trade-offs under conditions of high complexity and uncertainty, such as in GM agriculture.