This review discusses whole grain-gut microbiota interactions and identifies new areas of research that may contribute to a better understanding of the underlying mechanisms linked to human health. There is a growing recognition of the role of whole grains in modulating the composition and functional activity of the human gut microbiota, which, in turn, can impact host health. Specific components of whole grains, such as non-digestible carbohydrates and phenolic compounds, have been shown to modulate the gut microbiota. However, results from human intervention trials are not consistent in the specific taxa that are affected by whole grains. This may be because the composition of an individual's gut microbiota affects their response to whole grains. Although whole grains are good sources of non-digestible carbohydrates and phenolic compounds, not all of these substances are available for microbial fermentation. Increasing the proportion of substances available for microbial fermentation could improve the benefits of whole grains on human health outcomes that are mediated by gut microbiota.