Rabies remain a public health threat in Ghana, with implications extending beyond human health to livestock production, livelihoods, and economic security. Although dogs are the primary reservoirs, transmission to livestock poses challenges for disease surveillance, diagnosis, and control. This lecture presents epidemiological, clinical, and molecular findings from recent rabies investigations involving goats, pigs, and cattle. These include a goat farm outbreak and suspected cat involvement, molecular evidence of dog-to-bull transmission, and the first documented case of dog-associated pig rabies, resulting in human exposure during carcass processing. These cases highlight the complexity of cross-species transmission, gaps in community awareness, and vulnerabilities in zoonotic disease surveillance. The lecture looks into the role of One Health surveillance, intersectoral collaboration, targeted vaccination, and community engagement in strengthening disease prevention and control.