Infection of maize kernels by toxigenic fungi remains a challenging problem despite decades of research progress. Cultural practices, including crop rotation, tillage, planting date, and management of irrigation and fertilization, have limited effects on infection and subsequent mycotoxin accumulation. Current infrastructure and grain storage practices in developed countries can prevent postharvest development of mycotoxins, but this aspect remains a threat in developing countries, especially in tropical areas. Because most mycotoxin problems develop in the field, strategies are needed to prevent infection of growing plants by toxigenic fungi. Developing genetic resistance to Aspergillus flavus, Gibberella zeae, and Fusarium spp. (particularly F. verticillioides) in maize is a high priority. Sources of resistance to each of these pathogens have been identified and have been incorporated into public and private breeding programs. However, few, if any, commercial cultivars have adequate levels of resistance. Efforts to control infection or mycotoxin development through conventional breeding and genetic engineering are reviewed. The role of transgenic insect control in the prevention of mycotoxins in maize is discussed.