The objective of this paper is to provide a methodology to facilitate fulfilment of the regional agricultural potential of inland valleys in sub-Saharan Africa (SSA) such that local rural livelihoods are benefited and regional objectives of reducing poverty and increasing food safety are met, while safeguarding other inland-valley ecosystem services of local and regional importance. High-potential inland valleys should be carefully selected and developed and highly productive and resource-efficient crop production methods should be applied. This paper describes a participatory, holistic and localized approach to seize the regional potential of inland valleys to contribute to food security and poverty alleviation in sub-Saharan Africa. We analyzed over a 100 papers, reference works and databases and synthesized this with insights obtained from nearly two decades of research carried out by the Africa Rice Center and partners. We conclude that sustainable rice production in inland valleys requires a step-wise approach including: (1) the selection of 鈥?em>best-bet鈥?inland valleys, either new or already used ones, based on spatial modelling and a detailed feasibility study, (2) a stakeholder-participatory land use planning within the inland valley based on multi-criteria decision making (MCDM) methods and using multi-stakeholder platforms (MSP), (3) participatory inland-valley development, and (4) identification of local production constraints combining model simulations and farmer participatory priority exercises to select and adapt appropriate practices and technologies following integrated management principles.