The people of the United States and the world owe the United States Environmental Protection Agency (U.S. EPA) a debt of gratitude for preserving, protecting, and defending human health and the environment for the past half century. As we celebrate the 50th anniversary of the founding of the U.S. EPA, there are two truths about the agency that are difficult to deny: (1) U.S. EPA and its people constitute a renowned agency that has greatly improved both environmental and public health in the United States, and has served as the leading model for nations around the world; and (2) the approaches, tools, structures, and legal frameworks that created the achievements of the U.S. EPA must evolve-and grow-to deal with the issues facing the country and the planet in the next 50 years. Building on the creativity, innovation, and brilliance of individuals and groups working at the U.S. EPA over the course of the last half century, we present 10 recommendations organized in three areas: organization, paradigms, and strategies and tools. Underlying these recommendations are the frameworks of sustainability and systems thinking and guiding these recommendations is the goal of evolving the Environmental Protection Agency to the Environmental Prosperity Agency.