The uneven standards of surveillance, human- or animal-based, for zoonotic diseases or pathogens maintained and transmitted by wildlife H(R)s, or even domestic species, is a global problem, readily apparent even within the United States, where investment in public health, including surveillance systems, has a long and enviable history. As of 2006, there appears to be little scientific, social, or political consensus that animal-based surveillance for zoonoses merits investment in international infrastructure, other than the fledgling efforts with avian influenza, or targeted nontraditional avenues of surveillance and research. National institutions charged with strategic planning for emerging diseases or intentional releases of zoonotic agents have emphasized improving diagnostic capabilities for detecting human infections, modifying the immune status of human or domestic animals through vaccines, producing better antiviral or antibacterial drugs, and enhancing human-based surveillance as an early warning system. With the possible exception of extensive human vaccination, each of these approaches target post-spillover events and none of these avenues of research will have the slightest impact on reducing the risk of additional emergence of viruses or other pathogens from wildlife. Novel schemes of preventing spillover of human pathogens from animal H(R)s can only spring from improving our understanding of the ecological context and biological interactions of pathogen maintenance among H(R)s. Although the benefit derived from investments to improve surveillance and knowledge of zoonotic pathogens circulating among wildlife H(R) populations is uncertain, our experience with HIV and the looming threat of pandemic avian influenza A inform us of the outcomes we can expect by relying on detection of post-spillover events among sentinel humans.