Herpes zoster is a common condition that can have a significant impact on quality of life among older adults. A significant proportion of older subjects with herpes zoster develop post-herpetic neuralgia (PHN), a chronic condition that is difficult to treat. The Shingles Prevention Study was a large-scale clinical trial to determine the efficacy of a live, attenuated varicella zoster virus (VZV) vaccine ('zoster vaccine') for preventing or attenuating herpes zoster in subjects aged > or =60 years. A total of 38 546 subjects were given either zoster vaccine or placebo. The burden of illness (pain severity-by-duration), incidence of herpes zoster, and PHN decreased by 61.1%, 51.3% and 66.5% (all P<0.001), respectively, following vaccination. Vaccine efficacy was maintained for a 4-year follow-up period. A sub-study of the vaccine trial evaluated VZV-specific immunity in approximately 1200 vaccine or placebo recipients prior to vaccination, at 3 months and annually for 3 years. VZV-specific cell-mediated immunity (CMI) was boosted significantly by the zoster vaccine. This boost remained substantially intact for the 3 years of follow-up. It is likely that the vaccine-induced boost in VZV-specific CMI reversed the natural decline in these responses that occurs as part of the ageing process, thereby protecting vaccine recipients against herpes zoster and its complications.