By the year 2050, agriculture will have to provide the food and nutrition requirements of some 9 billion people. Moreover, to maintain that level of productivity indefinitely it must do so using environmentally sustainable production systems. This task will be profoundly complicated by the effects of climate change, increasing competition for water resources and loss of productive lands. Agricultural production methods will also need to recognize and accommodate ongoing rural to urban migration and address a host of economic, ecological and social concerns about the ‘high inputs/high outputs’ model of present-day industrial agriculture. At the same time, there is a need to confront the unacceptable levels of continuing food and nutrition insecurity, greatest in the emerging economy countries of Africa and Asia where poverty, rapid population growth and climate change present additional challenges and where agriculture is practiced primarily by small-scale farmers. Within this context, we here review science-based evidence arguing that diversification with greater use of highly valuable but presently under-valorised crops and species should be an essential element of any model for sustainable smallholder agriculture. The major points of these development opportunity crops are presented in four sections: agricultural farming systems, health and nutrition, environmental sustainability and prosperity of the populations. For each section, these crops and their associated indigenous knowledge are reported to bring benefits and services when integrated with food systems. In this paper, we conclude that not only a change in policy is needed to influence behaviours and practices but also strong leadership able to synergize the various initiatives and implement an action plan.