The effectiveness of risk mitigation may be compromised by informal trade, including illegal activities, parallel markets and extra-legal activities. While no regulatory system is 100% effective in eliminating the risk of disease transmission through animal and animal product trade, extreme risk aversion in formal import health regulations may increase informal trade, with the unintended consequence of creating additional risks outside regulatory purview. Optimal risk mitigation on a national scale requires scientifically sound yet flexible mitigation strategies that can address the competing risks of formal and informal trade. More robust risk analysis and creative engagement of nontraditional partners provide avenues for addressing informal trade.