Setting up an organ perfusion program faces many challenges and hurdles in translating ideas into a sustainable practice. As legal and logistical issues vary between centers, no perfect blueprint exists, although several cornerstones are key and should be considered by those looking to implement such programs. Programs should be developed according to local legal and ethical frameworks, considering the technology available, the added value that it brings, the adopter staff, and their willingness to change established clinical routines. This requires collaboration with policymakers and other key stakeholders in the wider healthcare system to ensure funding, regulatory approvals, and organizational resilience. The initiation of the programs often starts with small, dedicated teams that require training and expansion to build a sustainable service. Adaptation and flexibility are required to further improve local practice and enable the development of further complex programs such as TA-NRP and u-DCD.