This brief report serves as an introduction to a supplement of the Journal of Infectious Diseases entitled "Next-Generation Sequencing (NGS) Technologies to Advance Global Infectious Disease Research."We briefly discuss the history of NGS technologies and describe how the techniques developed during the past 40 years have impacted our understanding of infectious diseases. Our focus is on the application of NGS in the context of pathogen genomics. Beyond obvious clinical and public health applications, we also discuss the challenges that still remain within this rapidly evolving field.