When the pandemic influenza A (H1N1) 2009 virus emerged, one of the early priorities was to estimate its virulence. This is measured by the case-fatality ratio (CFR), the proportion of deaths from influenza among the total number of cases. Epidemiological studies in the very early stages of the pandemic estimated the confirmed CFR (cCFR), using confirmed cases as the denominator, to be approximately 0.5%. However, later studies estimated the symptomatic CFR (sCFR) as approximately 0.05% of all medically attended symptomatic cases. Although subjective, the virulence of influenza A (H1N1) 2009 can be perceived as mild. Further epidemiological investigations showed that both the cCFR and sCFR varied greatly by age and risk group. When assessing the efficacy of a specific intervention in reducing the risk of influenza-related death, particular care is required regarding the inclusion criteria and in matching age and underlying conditions between patients with, and without, the intervention. © 2010 Expert Reviews Ltd.