Interaction with the immune system is one of the most recently established non-classic effects of vitamin D (VitD) and recent reports have supported its role in promoting normal function of the innate and adaptive immune systems. Sub-optimal VitD status is a common peculiarity throughout the world and most particularly in the older population; a population presenting an increased susceptibility to infectious diseases and vaccine failure due to the age-related changes of the immune system commonly termed immunosenescence. This review will examine the current understanding of how VitD status may further impinge the immune senescence process. Furthermore, we discuss the role played by VitD in host immune response to common pathogens and to vaccinations.