Extensive tropical forest loss and degradation have stimulated increasing awareness at the international policy level of the need to undertake large-scale forest landscape restoration (FLR). Natural regeneration offers a cost-effective way to achieve large-scale FLR, but is often overlooked in favor of tree plantations. The studies presented in this special issue show how natural regeneration can become an important part of FLR and highlight the ecological, environmental, and social factors that must be considered to effectively do so. They also identify major knowledge gaps and outline a research agenda to support the use of natural regeneration in FLR. Six central questions emerge from these studies: (1) What are the ecological, economic, and livelihood outcomes of active and passive restoration interventions?; (2) What are the tradeoffs and synergies among ecological, economic, and livelihood outcomes of natural regeneration, restoration and productive land uses, and how do they evolve in the face of market and climate shocks?; (3) What diagnostic tools are needed to identify and map target areas for natural regeneration?; (4) How should spatial prioritization frameworks incorporate natural regeneration into FLR?; (5) What legal frameworks and governance structures are best suited to encourage natural regeneration and how do they change across regions and landscapes?; (6) What financial mechanisms can foster low-cost natural regeneration? Natural regeneration is not a panacea to solve tensions and conflicts over land use, but it can be advantageous under some circumstances. Identifying under what conditions this is the case is an important avenue for future research.