Improving and promoting global health continues to be one of the largest and most important challenges facing humanity in the twenty-first century. The task has become even more difficult since our first edition appeared almost a decade ago, given the accelerated destruction of the planet and the associated compounded threats to health that now present themselves. The emergence and spread of COVID-19 and the implications of this pandemic for life, health, and our planet exemplify how the world can change so rapidly and profoundly. The domino effects of the pandemic in an unstable global system are triggering multiple tipping points with implied radical alterations to the trajectory of life as we have known it. This is a stark reminder that despite all the major advances in science, healthcare, health, and longevity since the Enlightenment, and despite all the promises of genetic medicine and artificial intelligence, the long-term health and survival of our species are now, more than ever, intensely threatened.