From 2001 to 2010, an international effort was made through the implementation of two global projects aimed at enhancing the sustainable conservation and use of neglected and underutilized species (NUS). These projects represented the first UN-supported endeavors on NUS and tested out a novel collaborative framework involving all actors along the value chain of some representative target species (incl. Andean grains and minor millets). Stakeholders involved in the implementation of these projects ranged from scientists engaged in surveying, collecting, conserving and studying the genetic diversity of target species to farmers contributing to their maintenance in situ/on-farm, from breeders and experts working to develop better cultivars and value addition technologies to user groups, including women's associations. Nutritionists, school teachers and media experts were also active partners in implementing public awareness activities. Impact assessment studies have shown that these efforts have been highly successful, though challenging, with regard to maintaining effective and cohesive collaboration across so many different actors and groups with diverse interests. The key lesson learned from these efforts is that the NUS promotion requires, first and foremost, the adoption of a new R&D paradigm, directed towards cultural-sensitive objectives and not solely towards economic benefits. The promotion of NUS in any country, regardless of its state of development, is an opportunity to promote and make use of the crop diversity and associated food traditions present at the local level, which are the unique expression of the work of generations of farmers and users. Safeguarding such a heritage is an important contribution to protecting the identity of local communities and reinforcing their self-esteem and confidence to counteract threats of standardization of local food culture arising from globalization trends and changes in life styles. Essential in pursuing the use-enhancement of NUS is the adoption of multi-stakeholder, multi-disciplinary and participatory approaches. Because of the central role of women in deploying NUS diversity in everyday life, interventions to enhance their capacities in farming, adding value, marketing and cooking these species are critical. Furthermore, whereas better cultivars and technologies can help in making NUS economically more competitive, these projects have, however, shown that any increase in demands for such species and products can only be achieved once the food-of-the-poor stigma, that so often accompanies them, is effectively removed. Policies to develop standards in processing or promoting the inclusion of nutritious NUS in school feeding programs are also highly relevant. The role of multi-stakeholder platforms for promoting NUS is another important aspect emerging from these international efforts. A robust and gender-sensitive, capacity-building program for disseminating best practices and develop skills among users groups is essential for effective projects' exit strategies. The unabated genetic erosion of NUS, so poorly represented in ex situ germplasm collections, is also affecting the resilience and adaptation of traditional agro-ecosystems to climate change. Greater R&D attention on in situ conservation of NUS at the farm level is advocated through strategic interventions such as those supporting community-based participatory monitoring, custodian farmers' networks and crop diversity fairs.