Vitamin D is well known for its classic role in the maintenance of bone mineral density. However, vitamin D also has an important “non-classic” influence on the body’s immune system by modulating the innate and adaptive immune system, influencing the production of important endogenous antimicrobial peptides such as cathelicidin, and regulating the inflammatory cascade. Multiple epidemiological studies in adults and children have demonstrated that vitamin D deficiency is associated with increased risk and greater severity of infection, particularly of the respiratory tract. Although the exact mechanisms by which vitamin D may improve immune responses to infection continue to be evaluated, vitamin D supplementation trials of prevention and adjunct therapy for infection are underway. Given its influence on the immune system and inflammatory cascade, vitamin D may have an important future role in the prevention and treatment of infection.