Cross-sectional and longitudinal studies on vital statistics and population-based samples document that women live longer than men. The sex mortality differential covers all ages and races in most developed nations. The magnitude of the sex mortality differential varies with age, being especially high at younger ages. The most important contributor to the difference in mortality between women and men is the major cause of death in men, i.e., cardiovascular diseases. The universality of the sex mortality differential in various geographical areas, the lower female infant mortality, and the possible hormonal-mediated relative protection of CHD in women all indicate that biological factors contribute to the lower mortality in women than in men. Secular changes in mortality of various diseases over short periods cannot be explained by innate endogenous alterations but instead have to be influenced by behavioral factors and other components of the environment. Longstanding biological differences between women and men might play a role in producing a relatively rapid emergence of sex mortality differential only by interaction with relatively new exogenous environmental factors. The vast majority of studies on the sex differential in mortality trends confirm the importance of smoking as a major contributor to the higher mortality in men than in women. Along this line, other behavioral factors also seem to influence longevity in women. With ongoing changes in society, especially increasing participation of women in the labor force, new components of the environmental setting will have to be assessed by comparable and identical instruments in different populations. Ongoing monitoring of trends in cardiovascular and noncommunicable diseases will provide valuable insight into the sex mortality differential and its determinants. Experimental studies on biological reactivity, sex endocrinology, and atherogenesis are also needed to help explain why women live longer than men.