Varicella zoster virus (VZV) is the causative agent of chickenpox (varicella) and shingles (herpes zoster). In the course of these diseases VZV is able to productively infect a number of specialized cell types including T cells, dendritic cells, skin cells, ganglionic cells, and others. During infection, VZV also encodes a number of functions that modulate a range of immune evasion functions, and these are likely to enable this virus to limit the efficacy of both innate and adaptive arms of the anti-viral immune response. Despite the potent anti-viral capacity of natural killer (NK) cells, this cell type has not been studied in detail in the context of VZV infection. However, clinical evidence supports a crucial role for NK cells in the control of productive VZV infection as individuals with NK cell deficiency are highly susceptible to disseminated, life threatening VZV disease. We have observed NK cells in the immune infiltrate within naturally infected human ganglia following VZV reactivation. In addition, VZV infection of epithelial cells resulted in differential modulation of ligands for NKG2D (a potent activating receptor expressed on NK cells). Recently we identified NK cells as being highly permissive to productive VZV infection. This infection results in NK cell activation but impaired cytotoxicity and cytokine responses. These studies identify a cell type previously unrecognized as being permissive to VZV infection, and also reveal a complex manipulation of NK cell anti-viral function, whereby VZV impacts on both the NK cell itself and the cells it targets.