Excess body weight is a strong determinant as well as modifiable risk factor for all-cause and cancer mortality, and as such carries the potential for primary prevention. Recently published studies greatly enhance our knowledge about the impact of body fat distribution on relative risks specific to cancer type, and among women, there is further evidence for the role of menopausal status in modifying relative risks. However, the magnitude of all-cause as well as cancer mortality related to excess body weight varies between prospective cohort studies and the strength of the association, in particular in the overweight range, is still a matter of debate. The distribution of total body fat, how we measure it, and the ratio of body fat to fat-free mass explains to some degree the inconsistencies in associated disease risks in the literature. Physical activity, a potential confounder, has been shown to lower the risk of many chronic diseases, independently of the degree of adiposity. A review of the literature provides much support for public health messages that advocate the benefit of change to a more active lifestyle regardless of age and level of excess body fat.