Complex travel and transportation networks along with growing population mobility have contributed to the global proliferation of infectious diseases. Although human movement has always shaped the distribution and patterns of infectious diseases, today’s movement of human populations—unprecedented in volume, reach, and speed—has had particularly significant impacts on the spread of infectious disease. Complex travel and tourism networks, fueled by advances in transportation, technology, social media, and business along with increasing globalization have contributed to the reach and volume of passengers and goods carried around the world as well as to the movement of pathogens that is farther, faster, and in greater numbers than ever before. This chapter delves into the complex networks of travel, tourism and transportation in a globalized world, explores their role in disease proliferation, and introduces a complex-systems-grounded framework to the examination and control of infectious disease spread via travel, transportation and tourism. Viewing infectious disease within the context of global human mobility as a complex system offers an innovative and holistic perspective for examining disease dynamics and related impact factors and improves epidemiologists’ ability to understand, predict and mitigate infectious diseases.