Since its first synthesis in 1897, several medicinal roles and mechanisms of action of aspirin have become apparent; the latest among these being its role in cancer prevention and treatment. A large body of evidence supports aspirin's effect in reducing cancer incidence and cancer mortality, but duration of use needs to be at least 5 years. The beneficial effects are particularly large for colorectal, oesophageal and gastric cancers, with apparently smaller reductions for breast, prostate and lung cancer. The major harm is gastrointestinal bleeding, but serious sequelae are minimal at ages <70 years. It is very likely that use of prophylactic aspirin in the general population aged 50-70+ years will result in net overall benefit. Outstanding issues are: whether standard dose (~300 mg/day) can lead to greater net benefits than low dose (75-100 mg/day), the optimum duration of use, and appropriate ages for use in average-risk individuals.