Microbiologic and epidemiologic data on 1,933 cases of human listeriosis reported in England and Wales from 1990 to 2004 were reviewed. A substantial increase in incidence occurred from 2001 to 2004. Ten clusters (60 cases), likely to represent common-source outbreaks, were detected. However, these clusters did not account for the upsurge in incidence, which occurred sporadically, predominantly in patients ≥60 years of age with bacteremia and which was independent of sex; regional, seasonal, ethnic, or socioeconomic differences; underlying conditions; or Listeria monocytogenes subtype. The reasons for the increase are not known, but since multiple L. monocytogenes strains were responsible, this upsurge is unlikely to be due to a common-source outbreak. In the absence of risk factors for listeriosis in this emerging at-risk sector of the population, dietary advice on avoiding high-risk foods should be provided routinely to the elderly and immunocompromised, not just to pregnant women.