Throughout history, humankind has won the battle against deadly diseases, including small pox and polio, by defeating them through prevention. Cancer prevention is a global priority, but studying history suggests that the journey towards achieving this goal is difficult and full of detours and roadblocks. Epidemiology and clinical evidence clearly indicate that specific genetic, environmental and behavioural factors are associated with an increased risk for cancer development. What can we learn from the past that is applicable to the reality of successful cancer prevention?