The last few decades have been marked by a rapid expansion in the world?s population, along with an increasingly dynamic mobility of individuals. This accelerated global inter-connectedness enabled microorganisms to reach virtually any location worldwide more rapidly and efficiently than ever before, reshaping the global dynamics of pathogens. As a result, a local infectious disease outbreak anywhere in the world may almost instantaneously assume global dimensions, and should therefore be considered a global priority. The history of several infectious diseases illustrates that in addition to prophylactic and therapeutic medical interventions, the interplay of social, economic, and political factors makes a fundamental contribution to the outcome of infectious disease outbreaks. Furthermore, this multi- and cross-disciplinary interconnectedness is a key determinant of the outcome of efforts to eradicate vaccine-preventable infectious diseases. A combined framework that incorporates teachings provided by previous outbreaks, and integrates medical and biomedical interventions with contributions made by social, economic, and political factors, emerges as vital requirement of successful global public health initiatives.