Noroviruses are perhaps the perfect human pathogens. These viruses possess essentially all of the attributes of an ideal infectious agent: highly contagious, rapidly and prolifically shed, constantly evolving, evoking only limited immunity, and just moderately virulent, allowing most of those infected to fully recover, thereby maintaining a large susceptible pool of hosts. These characteristics have enabled noroviruses to become the leading cause of endemic diarrheal disease across all age groups, the leading cause of foodborne disease, and the cause of half of all gastroenteritis outbreaks worldwide. In the United States alone, noroviruses are responsible for an estimated 21 million cases of acute gastroenteritis annually, including >70,000 hospitalizations and nearly 800 deaths. In developing countries, where the greatest burden of diarrheal disease occurs, noroviruses have been estimated to cause up to 200 000 deaths each year in children <5 years of age. Although recognition of this immense disease burden is relatively recent, it is unclear whether it has long been present and failed to be recognized because of lack of sensitive diagnostics or if, in fact, noroviruses represent a truly emergent public health issue. Regardless, attempts to address the overwhelming burden of norovirus disease first require an understanding of the complexity and efficiency with which these viruses spread.