Human-to-human transmissible pandemics, most notably the Medieval Black Death and Spanish Flu of 1918, have historically resulted in the world’s greatest mortality events. Today, as global transportation networks move people rapidly around the world, there are few barriers to emergent diseases. The mystery of the next great pandemic is not if, but rather when and where it will emerge. Therefore, understanding basic epidemiological attributes of infection, and the highly variable matrix of political, economic, and cultural attributes which affect micro-scale disease transmission, is now more critical than ever. An emergent disease has the capacity to become a deadly global pandemic if optimized for infectivity, lethality, and environmental persistence. Lacking optimization in any one of these broad attributes can lead to a disease that is technically a pandemic with high infectivity, yet exhibits low lethality, such as Swine Flu (H1N1). In addition, a disease could emerge with very high lethality, yet which does not persist in the environment very long outside of a host, nor kills slow enough to allow for a large amount of secondary infections to occur from contact with a primary infected host, similar to the Ebola virus in Sub-Saharan Africa. The spatial dynamics of emergent diseases is also affected by socioeconomic processes such as the built environment, migration, poverty, race, ethnicity, and gender relationships. Yet even with so many variables present, super-spreading events, whereby a few infected individuals secondarily infect a high number of susceptible individuals, can rapidly transmit infectious diseases across very heterogeneous spaces. Today’s global social networks and connectivity are leading toward an enhanced potential for pandemic infections and greater disease virulence as a bio-evolutionary consequence toward pathogenic success.