The COVID-19 pandemic of acute respiratory disease caused by SARS–CoV-2 coronavirus (CoV) is an unparalleled event that harkens back to days before viruses could be seen or understood. HIV-1 arose as a regional zoonotic disease during the last century and evolved into a global crisis of enormous proportions; it was nearly universally fatal, but its global spread and disease progression were relatively slow, and it was perceived as being more escapable. More recent outbreaks, such as Ebola in West Africa and Eastern Congo and MERS-CoV in the Middle East were characterized by high mortality rates and rapid spread, but remained relatively contained regionally, with only episodic global spread. The arboviruses, Zika and chikungunya, caused devastating disease with long-lasting effects, but did not cause high mortality and were geographically limited by the range of their vectors. During the last century, the world has endured threats from avian influenza and pandemic influenza, but neither led to shutting down of society to the extent experienced with COVID-19. Uniquely, COVID-19 is caused by a newly discovered CoV strain and part of a virus family that many people had not heard of before, has substantial human-to-human transmission through respiratory secretions, has spread globally within a matter of weeks, affects individuals from all levels of society and status, and has a high enough morbidity and mortality to overwhelm our health care systems. Therefore, it has galvanized public interest in pandemic threats as no other virus has before.