Outbreaks of foodborne illness associated with the consumption of leafy green produce from California and across the United States have heightened the need to identify vertebrate sources of these microbial hazards. Concern has focused on wildlife species that have direct access to the produce production environment and irrigation water supplies. Recent fecal surveys of California wildlife, feral animals, and livestock and companion animals are allowing regulators to compare the food safety risks of such pathogens as E. coli O157:H7 and Salmonella from these various animal species. In order to make valid food safety risk comparisons between wildlife, livestock, and companion animals, a variety of methodological and epidemiological issues need to be addressed in order to avoid substantial biases. For example, the amount of feces tested per animal can vary up to a 1000-fold, substantially biasing the probability of testing positive for large fecal contributors (e.g., cattle) compared to smaller wildlife (e.g., deer mice). Many wildlife species intrude and forage as a group in fields of produce, which can lead to in-field defecation, substantially, elevating the risk of microbial contamination compared to many larger animal species that do not have direct access to produce fields due to fencing. This paper highlights the technical challenges of making valid quantitative comparisons of microbial food safety risks from wildlife compared to other domestic animals.