Sixteen pandemic months have felt disorienting and arduous—but along the arc of human history, COVID-19 marks just another inflection point. Epidemics have punctuated humanity’s timeline for centuries, sowing panic and killing millions of people, whether the culprit was plague or smallpox or influenza. And when infections abate, their imprints on society can remain, some short-lived and some enduring. In a series of news articles over the coming months, Science will consider how a new normal is emerging in the scientific world. Of course, COVID-19 is still with us, especially outside the minority of countries now enjoying the fruits of widespread vaccination. Still, as the pandemic enters a new phase, we ask how research may be changing, how scientists are navigating these waters, and in what directions they are choosing to sail. Although past may not presage the future, epidemic history illuminates how change might unfold.