In Western societies, energy imbalance is characterized by obesity and sedentary life styles and is associated with increased morbidity and mortality from all causes of cancer, including cancer of the breast, colon and prostate. The interrelationships of energy intake and energy retention, to energy expenditure and physical fitness need further investigation from the physiologic, metabolic, endocrine and genetic aspects of cancer development, since obesity, energy expenditure and cancer have a familial predisposition. The effects of exercise on estrogen and prostaglandin metabolism and their relationship to cancer development require further investigation. Although the exact amount and intensity of exercise that confers benefit is not known, physical activity and physical fitness are inversely associated with all-cause mortality, including cancer. These findings have important public health implications, because about one-third of persons in industrialized societies are quite sedentary, and the prevalence of low physical fitness is quite high. The balance between total energy intake and expenditure may be more important in cancer development than the intake of any given dietary component or energy source. Exercise increases prostacyclin and decreases the aggregation of platelets and possibly decreases the platelet derived growth factors (PDGF). One could speculate that exercise may in turn decrease the probability of developing colon cancer in those who are predisposed to it, since the SIS oncogene is in fact a variant of PDGF.