Evidence is accumulating that high levels of physical activity are associated with a reduced risk of some cancers. This evidence is most consistent for colon cancer, which is reduced by 40–50 % among the most active individuals, compared with the least active. The effect is evident in men and women, and appears to be independent of important confounding factors. However, there may be important interactions with body fatness; a high BMI has been reported to be associated with an increased risk of colon cancer in sedentary men but not in physically-active men. Whilst the evidence on breast cancer is less consistent, case–control studies typically suggest a reduction of 25–30 % among the most active women, although several studies have found no effect. Potential mechanisms include systemic influences and others relevant only to site-specific cancers. One unifying hypothesis is that physical inactivity reduces insulin sensitivity, leading to a growth-promotional environment which may facilitate neoplasia. The non-specific immune system may be improved by physical activity, possibly through the summative effects of repeated exercise bouts. Regular exercise, even at a recreational level, probably reduces exposure to oestrogen and thus decreases the risk of breast cancer. Increased colonic peristalsis, and thus reduced bowel transit time, might partly explain the lower risk of colon cancer in active people. Physical activity emerges as one of the few modifiable risk factors for some cancers and, as such, justifies further study.