Disease prevention can be defined as measures that seek to avert the occurrence of disease (including injury), arrest its progress, and reduce its consequences once it is established. Disease prevention can be classified into levels: primordial, primary, secondary, and tertiary prevention. Preventive interventions aim at interrupting the web of causality leading to one or more aspects of ill-health. They are directed at different phases in the development of disease, aiming at eradicating, eliminating, or minimizing its impact, or if none of this is feasible, retarding the progress of disease and disability. Building on the model of disease causation this article illustrates the different levels of disease prevention and describes core strategies toward prevention, juxtaposing the high-risk strategy and the population strategy of prevention as first outlined by Geoffrey Rose. It illustrates the challenges related to disease prevention using examples of noncommunicable diseases and injuries, drawing on both successes and failures of different preventive approaches. It then discusses some fundamental aspects of prevention as they relate to ethical considerations and the evidence base of preventive intervention. The article closes with a brief reminder that decisions made outside the health-care sector can have major consequences for population health and discusses its implications for disease prevention.