Threats posed by new, emerging or re-emerging communicable diseases are taking a global dimension, to which the World Health Organization (WHO) Secretariat has been responding with determination since 1995. Key to the global strategy for tackling epidemics across borders is the concept of global public health surveillance, which has been expanded and formalized by WHO and its technical partners through a number of recently developed instruments and initiatives. The adoption by the 58th World Health Assembly of the revised (2005) International Health Regulations provides the legal framework for mandating countries to link and coordinate their action through a universal network of surveillance networks. While novel environmental threats and outbreak-prone diseases have been increasingly identified during the past three decades, new processes of influence have appeared more recently, driven by the real or perceived threats of bio-terrorism and disruption of the global economy. Accordingly, the global surveillance agenda is being endorsed, and to some extent seized upon by new actors representing security and economic interests. This paper explores external factors influencing political commitment to comply with international health regulations and it illustrates adverse effects generated by: perceived threats to sovereignty, blurred international health agendas, lack of internationally recognized codes of conduct for outbreak investigations, and erosion of the impartiality and independence of international agencies. A companion paper (published in this issue) addresses the intrinsic difficulties that health systems of low-income countries are facing when submitted to the ever-increasing pressure to upgrade their public health surveillance capacity.