Whereas those who live in the native ranges of the large feline carnivores are well aware of the risks of cat and human encounters, North Americans and Europeans are increasingly exposed to exotic animals through travel, ecotourism, leisure pursuits in rural areas, occupational exposure, zoo and animal park visits, wild habitat encroachment at the urban-wildlands interface, and contact with exotic pets. In encounters during which persons have been severely injured, lapses in animal management protocols, lack of appropriate adult supervision, and intoxication have been reported. Unlike common domestic pets that have lived in close association with humans for thousands of years, no matter where individual large felines may have been raised, they remain wild carnivores with strong prey-drive and territorial instincts. The emergency management of large felid attacks is similar to that of other major trauma: stabilization; management of significant orthopedic, neurologic, vascular, and soft tissue injuries; antibiotic coverage provided for the number of organisms that inhabit their mouths and the potential for tetanus and rabies; and early management in survivors of likely posttraumatic stress disorder. We must actively explore responsible measures globally that can be taken to ensure biologically appropriate, ethical, safe, and sustainable conservation of these large carnivores in both their natural habitats and captivity.