The proverbial benefits of prevention over cure are self-evident—and yet we are reluctant to invest in staying healthy. Resolution of this age-old dilemma begins with a timeless truth: the benefits of good health come at a cost: prevention is not better than cure at any price. That logic leads to a testable—and refutable—proposition: that prevention should be favoured when an imminent, high-risk, high-impact hazard can be averted at relatively low cost. Application of this idea helps to explain why cigarette smoking is still commonplace, why the world was not ready for the COVID-19 pandemic, why the idea of a ‘sin tax’ is misconceived, why billions still do not have access to safe sanitation, why the response to climate change has been so slow, and why public health advice often falls on deaf ears. Much more money and effort are invested in health promotion and prevention today than is commonly thought, but the enormous avoidable burden of illness is reason to seek incentives for investing still more. The principles, together with a series of case studies in diverse settings, offer 12 lessons for prevention. These are methods and motives for shifting the balance away from reactive medical treatment, bypassing illness and injury, to promote better health and well-being.