The Congressionally Directed Medical Research Programs (CDMRP) is a collection of 18 individual programs that seek to find and fund the best research to eradicate diseases and support the warfighter for the benefit of the American public. In fulfilling its mission, CDMRP emphasizes innovative, high-risk, high-gain research that might otherwise not be funded and projects that forge new collaborations in furtherance of important research objectives. Research proposals (applications) are reviewed using a two-tiered process that includes peer review panels that evaluate scientific merit, innovation, and impact, followed by an external review that makes funding recommendations based on programmatic intent and portfolio balance. At both levels of review, CDMRP's processes are distinguished by the inclusion of consumer advocates, who are integral to the program's ability to focus on research that will have an impact on the communities affected by the relevant illness, injury, or disorder. Scientific peer review is executed using a dynamic and flexible process and produces a robust and comprehensive summary statement that serves as the basis for the second tier of review, informs subsequent award negotiations, and provides valuable feedback to all applicants. In combination with a strong commitment to integrity and transparency, CDMRP's peer review processes support the organization's mission to fund innovative, high-impact research.