Commercialization of genetically modified organisms (GMOs) have sparked profound controversies concerning adequate approaches to risk regulation. Scientific uncertainty and ambiguity, omitted research areas, and lack of basic knowledge crucial to risk assessments have become apparent. The objective of this article is to discuss the policy and practical implementation of the Precautionary Principle. A major conclusion is that the void in scientific understanding concerning risks posed by secondary effects and the complexity of cause-effect relations warrant further research. Initiatives to approach the acceptance or rejection of a number of risk-associated hypotheses is badly needed. Further, since scientific advice plays a key role in GMO regulations, scientists have a responsibility to address and communicate uncertainty to policy makers and the public. Hence, the acceptance of uncertainty is not only a scientific issue, but is related to public policy and involves an ethical dimension.