Several studies have documented the impact of vitamin D and other micronutrients on host responses to upper and lower respiratory tract infections, such as influenza and tuberculosis. These studies include observational as well as micronutrient intervention studies. Other studies have been conducted to understand the mechanisms by which micronutrients alter immune responses. However, critical information gaps and challenges remain. An immediate need exists for randomized controlled trials of vitamin D supplementation in high-risk populations, such as infants, children, and patients with immunocompromised health. Other important areas of research include vitamin D genetics, the impact of other micronutrient deficiencies on innate and adaptive immunity, the 25(OH)D threshold for insufficiency, the need for valuable reliable markers, standardization of assays to detect 25(OH)D, novel functional markers beyond serum 25(OH)D, and further development of in vitro and animal models that could be useful for preclinical studies. Lastly, a new systems biology approach is needed to address the complexity of micronutrient effects and regulation.