New information about the mechanisms of varicella-zoster virus (VZV) pathogenesis and the host response to the virus has improved our understanding of the threat that VZV reactivation may pose after hematopoietic cell transplantation (HCT). Antiviral therapy compensates for some of the deficiencies in VZV immunity in HCT recipients, and inactivated varicella vaccine may be useful for the early reconstitution of adaptive immunity to VZV after HCT.