Vitamin D has become increasingly recognized in the literature for its extra-skeletal roles, including an effect on inflammation and the immune response to infection. Our goal was to describe the role of vitamin D in the immune response and implications for the risk of influenza infection in humans. In this review, we first consider literature that provides molecular and genetic support to the idea that vitamin D is related to the adaptive and innate immune responses to influenza infection in vitro and in animal models. We then discuss observational studies and randomized controlled trials of vitamin D supplementation in humans. Finally, we consider some of the knowledge gaps surrounding vitamin D and immune response that must be filled.