Modern agricultural systems that promote cultivation of a very limited number of crop species have relegated indigenous crops to the status of neglected and underutilised crop species (NUCS). The complex interactions of water scarcity associated with climate change and variability in sub-Saharan Africa (SSA), and population pressure require innovative strategies to address food insecurity and undernourishment. Current research efforts have identified NUCS as having potential to reduce food and nutrition insecurity, particularly for resource poor households in SSA. This is because of their adaptability to low input agricultural systems and nutritional composition. However, what is required to promote NUCS is scientific research including agronomy, breeding, post-harvest handling and value addition, and linking farmers to markets. Among the essential knowledge base is reliable information about water utilisation by NUCS with potential for commercialisation. This commentary identifies and characterises NUCS with agronomic potential in SSA, especially in the semi-arid areas taking into consideration inter alia: (i) what can grow under water-scarce conditions, (ii) water requirements, and (iii) water productivity. Several representative leafy vegetables, tuber crops, cereal crops and grain legumes were identified as fitting the NUCS category. Agro-biodiversity remains essential for sustainable agriculture.