One-health approaches have started being applied to health systems in some countries in controlling infectious diseases in order to reduce the burden of disease in humans, livestock and wild animals collaboratively. However, one wonders whether the problem of lingering and emerging zoonoses is more affected by health policies, low application of one-health approaches, or other factors. As part of efforts to answer this question, the Southern African Centre for Infectious Disease Surveillance (SACIDS) smart partnership of human health, animal health and socio-economic experts published, in April 2011, a conceptual framework to support One Health research for policy on emerging zoonoses. The main objective of this paper was to identify which factors really affect the burden of disease and how the burden could affect socio-economic well-being. Amongst other issues, the review of literature shows that the occurrence of infectious diseases in humans and animals is driven by many factors, the most important ones being the causative agents (viruses, bacteria, parasites, etc.) and the mediator conditions (social, cultural, economic or climatic) which facilitate the infection to occur and hold. Literature also shows that in many countries there is little collaboration between medical and veterinary services despite the shared underlying science and the increasing infectious disease threat. In view of these findings, a research to inform health policy must walk on two legs: a natural sciences leg and a social sciences one