Vitamin D’s non-skeletal actions, including immunomodulatory role, have been increasingly recognized. Of significance, many immune cells are able to synthesize a biologically active form of vitamin D from circulating 25-(OH) D with subsequent intracrine actions, and the vitamin D receptor (VDR) is broadly distributed. In this review, we discuss vitamin D’s potent role in innate and adaptive immune responses and published studies evaluating the impact of serum vitamin D, vitamin D gene pathway polymorphisms or empiric vitamin D supplementation on vaccine immunogenicity. We highlight existing knowledge gaps and propose the steps needed to advance the science and answer the question of whether vitamin D may prove valuable as a vaccine adjuvant for certain vaccines against infectious diseases.