This article builds on recent field research to articulate a principle-based approach to environmental regulatory design that is applicable to a wide variety of circumstances, irrespective of political and social particularities. At its core, this approach recognizes that an excessive reliance on “single-instrument” policies is misguided, because all instruments have strengths and weaknesses, and none is sufficiently flexible and resilient to successfully address all environmental problems in all contexts. A better strategy is to harness the strengths of individual mechanisms while compensating for their weaknesses by the use of additional instruments. That is, in the large majority of circumstances, a mix of regulatory instruments is required, tailored to specific policy goals. The article identifies a series of regulatory design principles that sequentially address the problems and opportunities arising from the application of multi-instrument mixes and engaging a variety of first-, second-, and third-party participants in the regulatory process. The importance of choosing inherently complementary instrument combinations is also highlighted, with practical guidance provided to policymakers. Although the focus of the article is on environmental regulation, the general principles articulated should also be applicable to other areas of social regulation.