The US and the EU have taken different paths in the design and implementation of biofuel support and enforcement measures. In the EU, indicative targets have been defined for biofuels, but a strict enforcement mechanism does not exist in practice. Also, mandatory targets have been approved voluntarily by several EU Member States. US biofuel policy has specified targets in absolute quantities rather than in percentages of use, as was done in the EU. Because of this quantitative target and the fact that enforcement is through a mandate rather than a less binding target, enforcement is assured but implementation problems arise (e.g., “blend wall”) that may not occur in the EU system. In this paper, we provide an analytical discussion on lessons learned from the current and previous EU and US biofuel enforcement mechanisms and consider the possibilities, opportunities and challenges for future policy development in both economies.