Scientific evidence is accumulating on physical activity as a means for the primary prevention of cancer. Nearly 170 observational epidemiologic studies of physical activity and cancer risk at a number of specific cancer sites have been conducted. The evidence for decreased risk with increased physical activity is classified as convincing for breast and colon cancers, probable for prostate cancer, possible for lung and endometrial cancers and insufficient for cancers at all other sites. Despite the large number of studies conducted on physical activity and cancer, most have been hampered by incomplete assessment of physical activity and a lack of full examination of effect modification and confounding. Several plausible hypothesized biological mechanisms exist for the association between physical activity and cancer, including changes in endogenous sexual and metabolic hormone levels and growth factors, decreased obesity and central adiposity and possibly changes in immune function. Weight control may play a particularly important role because links between excess weight and increased cancer risk have been established for several sites, and central adiposity has been particularly implicated in promoting metabolic conditions amenable to carcinogenesis. Based on existing evidence, some public health organizations have issued physical activity guidelines for cancer prevention, generally recommending at least 30 min of moderate-to-vigorous intensity physical activity on > or =5 d/wk. Although most research has focused on the efficacy of physical activity in cancer prevention, evidence is increasing that exercise also influences other aspects of the cancer experience, including cancer detection, coping, rehabilitation and survival after diagnosis.