Although the threat of pandemic influenza, spawned by continuing avian influenza A (H5N1) epidemics, has dropped off the front pages, concern among experts continues to grow. At the end of 2005, only 17 countries had H5N1 outbreaks in chickens, ducks, or humans [1]. As of September 2007, the virus has circulated in 60 countries [1], mutations have been reported (for example, in a patient in Turkey [2] and another in Thailand [3]), and virologists and public health officials nervously watch clusters of probable human-to-human spread of the virus, such as in Thailand in 2004 and Indonesia in 2006 [4]. For reasons not fully understood, most human cases and clusters of probable human-to-human transmission of H5N1 since January 2006 have occurred in Indonesia [5,6]. Recent studies have begun to characterize the mutations in H5N1 that may be a prerequisite for efficient human-to-human transmission [7,8]. The world needs to monitor each new influenza virus in order to check for such mutations, which could transform H5N1 into a dangerous pathogen easily spread between people. How devastating might such a transformation be? In an age of globalization and commercial air travel, estimating how great a toll a lethal human-to-human influenza virus could inflict is difficult. Estimates of deaths from the last great bird-to-human flu pandemic of 1918 range from 50 to 100 million [9], which provides a glimpse of the global damage that could be caused by a pandemic influenza accelerated by 21st century globalization.