The proliferation resistance and physical protection evaluation methodology provides a structured approach to assess a nuclear energy system's capability to respond to security challenges. The methodology applies a threat/system response/outcome framework to identify and characterize potential system vulnerabilities, and to guide designers toward system designs that minimize or eliminate these vulnerabilities. Application of the methodology during conceptual design provides an opportunity to develop functional requirements and design bases that can be used subsequently in the detailed design to achieve high proliferation resistance and physical protection robustness. This paper reviews the major elements of the methodology, including insights from recent studies using the methodology.