Evidence clearly shows that magnesium and vitamin D [1 alpha, 25-dihydroxyvitamin D3; 1,25(OH)2D3] independently affect numerous aspects of the immune system. Although no reports of interactive effects on components of immunity have been found, there is evidence that the two nutrients interact in other biosystems, sometimes involving calcium. Furthermore, this paper identifies numerous places in common where both magnesium and vitamin D reportedly affect immune function. Fundamental sites for possible interaction within the immune system include cell transformation, regulation of the cell cycle, stabilization of nuclear DNA/chromatin, production of reactive oxygen species (ROS), and effects on enzymatic and hormonal actions. The presence of different functional, chemical forms of both of the nutrients within biological systems, and the availability of synthetic drug relatives of both to introduce into such systems, complicate interactive studies because such differing forms may not necessarily interact similarly or interact at all within the immune system or elsewhere. Regardless, there are compelling reasons to believe that examining interactions between magnesium and vitamin D within the immune system could prove rewarding, especially since the physiological statuses of both nutrients in human populations are less than optimum. Such human populations include the elderly whose immune function may be compromised.