Very Large Research Infrastructures (VLRIs) are unique, complex undertakings with a strong international dimension that play a critical role in frontier research in most scientific domains. VLRIs require considerable care in their construction and operation, as well as very substantial investments and technological innovations. Recent evolutions in the political, socio-economic and scientific context are challenging their established planning and management models. This policy report identifies and analyses good practices and presents a series of lessons learned regarding the establishment of VLRIs, options for improving their use and operation, as well as more strategic considerations that VLRI managers, funders and decision-makers should take into consideration.