We introduce the empirical papers in this special issue, each of which presents a different mode of speculation in the context of living with, and caring for, chronic conditions: “educated guesswork” about covid reinfection, “ambivalent speculations” in learning to live “at risk” with Barrett’s Esophagus and “retrospective speculation” in pressure ulcer prevention. We reflect on how they together contribute to current thinking on the politics of time in health and medicine, and wider conversations in medical anthropology and beyond, about chronic illness as both a lived everyday reality and part of an unfolding, unpredictable collective future.