Context: Sorghum, an ancient grain originating in Africa, may have health-protective properties that could encourage its consumption among those who do not traditionally consume it. Objective: The aim of this systematic review was to evaluate the health effects associated with the consumption of sorghum among humans. Data Sources: Academic databases were searched for relevant studies published between 1985 and November 2015. Study Selection: Nineteen studies –13 interventional and 6 observational – were identified for inclusion. Data Extraction: Participant characteristics, study country, health outcomes, main findings, and study quality were reported. Interventional and observational studies were summarized separately. Results: Studies were divided into those that investigated the effect of sorghum on chronic disease and those that investigated other effects of sorghum on health. There was evidence that the consumption of sorghum attenuated blood glucose responses and decreased the expression of markers of oxidative stress. Sorghum was also observed to be a suitable ingredient for the formulation of oral rehydration solutions and showed potential for use as a medical adjunct to boost immune responses in HIV-positive patients . Conclusions: The implication is that sorghum may have attributes superior to those of other staple grains, indicating its potential for innovative uses in commercial foods. More work is required to elucidate the health effects of sorghum when consumed by population groups that have not been traditional consumers of the grain.