Agriculture in Africa south of the Sahara (SSA) is still largely rainfed. SSA also exhibits the lowest crop yields for major staples in the world, largely due to low use of irrigation and fertilizer. Rainfed agriculture poses growing production risks with increased climate variability and change. At the same time, smallholder irrigation in the region developed rapidly over the past decade, albeit starting from very low levels. In addition to largely demand-driven irrigation development by smallholders, there is a significant push by donors for large-scale irrigation development, as well as some push for smallholder irrigation. There has also been a long-standing debate about whether irrigation in SSA should be large scale or small scale to achieve its potential. However, given the potentially high rewards, but also high possibility of failure, the assessment of irrigation potential must go beyond large scale versus small scale to integrate concerns regarding environmental sustainability, resource use efficiency, nutrition and health impacts, and women’s empowerment. The hypothesis underlying this review paper is that how irrigation gets deployed in SSA will be decisive not only for environmental sustainability (such as deciding remaining forest cover in the region) and poverty reduction, but also for health, nutrition, and gender outcomes in the region. The focus of this paper is on the health, nutrition, and gender linkage. We find that to date, few studies have analyzed the impact of irrigation interventions on nutrition, health, and women’s empowerment, despite the large potential of irrigation to affect these important variables. Irrigation interventions may have differential effects on different members in the household and in the community, such as irrigators, non-irrigators, children, and women. Measuring and understanding such differences, followed by improving design and implementation to maximize gender, health, and nutrition outcomes, could transform irrigation programs from focusing solely on increased food production toward becoming an integral component of poverty-reduction strategies.