Infectious diseases of agricultural animals can have devastating impacts on economies (income, food security, and trade), the environment (wildlife die-offs), and societies (community stability and social unrest), and could threaten a country’s security interests or degrade its international and trade relationships. Animal diseases also have major implications for personnel and equipment movements (such as movement of military forces and vehicles), which increasingly are recognized as potential long-range dissemination pathways. The worldwide growth and connectivity of livestock production may heighten the risk of transnational contagion, with new opportunities for pathogen transmission at the wildlife interface and within and between agricultural facilities. Current approaches to modeling the emergence and spread of livestock diseases tend to focus on selected modes of transmission and settings, but typically do not consider transmission pathways that may be rare but important for long-range pathogen dissemination. Also current efforts may not adequately account for the role of environmental variation and change in disease emergence and spread. More detailed data and comprehensive models are needed to understand and predict livestock disease dynamics, particularly low-probability, high-consequence dissemination of virulent pathogens to new settings.