Varicella zoster virus (VZV) is a medically important human alphaherpesvirus and the causative agent of varicella (chickenpox) and herpes zoster (shingles). Clinical observations from natural killer (NK) cell deficient patients have identified a crucial role for NK cells in controlling infection, with such patients extremely susceptible to life-threatening infection with human herpesviruses, in particular, VZV. Despite this critical role for NK cells, understanding of how VZV interacts with NK cells is extremely limited. In our study, we examined NK cell activation by VZV through co-incubating human NK cells with VZV infected target cells and assessing surface expression of the degranulation marker, CD107a. Flow cytometric analysis revealed that VZV was capable of restricting activation of NK cells, implying extensive immune modulation. To further elucidate how VZV may be interacting with NK cells, we investigated viral regulation of ligands for the NK cell activating receptor, NKG2D. At the transcript and protein level VZV induced expression of NKG2D ligands, however a significant decrease in cell-surface expression was consistently observed, suggesting an immunomodulatory activity of VZV to retain these molecules within infected cells. In understanding how VZV is able to control NK cell activation, we also examined whether VZV has the capacity to infect human NK cells. Analysis by flow cytometry revealed the first finding that human NK cells are highly permissive to VZV infection, with 40% of cells identified as VZV antigen positive. In contrast, T cells, which are a known site of productive VZV infection, were confirmed to show a 10-15% infection rate in accordance with previous studies and highlighting the enhanced tropism experienced with NK cells. This finding thus identifies a cell type previously unrecognised as permissive to infection, and poses significant implications for our knowledge of VZV pathogenesis and the effect of infection on NK cell function.