Vitamin D plays a pivotal role in calcium homeostasis and bone metabolism.  However, studies over the last 25 years suggest that the biological impact of vitamin D extends far beyond the skeleton to include potent anticancer, antihypertensive and immunomodulatory effects.  The latter are particularly interesting given the historical link between vitamin D and infectious diseases such as tuberculosis and leprosy.  More recent studies have shown that vitamin D can influence key mechanisms associated with both the innate and adaptive arms of the immune system.  Many cells within the within the classical immune system, as well as associated non-classical immune targets such as epithelial and stromal cells express the nuclear vitamin D receptor (VDR) that binds the active form of vitamin D, 1,25-dihydroxyvitamin D (1,25D).  In addition, antigen presenting cells such as macrophages and dendritic cells (DCs) are capable of synthesizing 1,25D from precursor 25-hydroxyvitamin D (25D) by expressing the activating enzyme 1α-hydroxylase (CYP27B1).  Synthesis of 1,25D by macrophages or DCs may support endogenous intracrine responses (notably the induction of antibacterial proteins in macrophages), but may also involve paracrine actions (notably phenotype effects on VDR-expressing T-cells).  Crucially, all of these effects are highly dependent on the availability of the substrate for CYP27B1, 25D, which is also the main marker of vitamin D status in any given individual.  Based on this it has been proposed that vitamin D-deficiency may have profound effects on infection and immunity.  The aim of this presentation will be to explore this link between the vitamin D and the immune system in greater detail, with specific emphasis on novel immunomodulatory mechanisms, disease-specific corruption of vitamin D responses and the scope for clinical intervention through vitamin D supplementation.