Biotechnology applications such as the use and production of genetically modified organisms (GMOs) have been widely promoted, adopted, and employed by agricultural producers throughout the world. Yet, little research exists that examines the implications of agricultural biotechnology on the health and safety of workers involved in agricultural production and processing. Regulatory frameworks do exist to examine key issues related to food safety and environmental protection in GMO applications. However, based on the lack of research and regulatory oversight, it would appear that the potential impact on the safety and health of workers is of limited interest. This article examines some of the known worker health and safety implications related to the use and production of GMOs using the host, agent, and environment framework. The characteristics of employers, workers, inputs, production practices, and socio-economic environments in which future agricultural workers perform various tasks is likely to change based on the research summarized here.