This paper reviews evidence concerning genetic factors that influence sex differences in human mortality, with attention to the interactions between genetic and environmental factors. Some widely quoted earlier conclusions, for example, that males have consistently higher fetal mortality than females, are not supported by current evidence. For example, for late fetal mortality, males had higher rates than females in earlier historical data, but not in recent data for several advanced industrial countries. This reflects a changing balance between an inherently greater female vulnerability for one major type of late fetal mortality and inherently greater male vulnerability for several other types of late fetal mortality that have declined in importance as health care has improved. Males appear to be inherently more vulnerable than females to infant mortality, although the causes of this vulnerability are poorly understood. X-linked immunoregulatory genes appear to contribute to greater female resistance to infectious diseases. Despite these apparent inherent advantages for females, in some situations females have had higher infant mortality and higher infectious disease mortality than males, apparently due to environmental disadvantages for females, such as less adequate diet and health care. Inherent sex differences in reproductive physiology and anatomy contribute to higher female mortality for breast cancer and maternal mortality. For these causes of death, as for the other categories discussed, the death rates and thus the contributions to sex differences in total mortality vary considerably depending on environmental conditions. Several hypothesized contributions of sex hormones to sex differences in mortality are at present controversial due to contradictions and limitations in the available data. There may be effects of male sex hormones on sex differences in behavior which contribute to males' higher death rates for accidents and other violent causes. Women's endogenous sex hormones may reduce women's risk of ischemic heart disease. For both violent deaths and ischemic heart disease it appears that any genetic contributions to sex differences in mortality are strongly reinforced by the cultural influences that foster more risky behavior in males, including more use of weapons, employment in hazardous occupations, heavy alcohol consumption and cigarette smoking. It appears that these cultural influences on sex differences in behavior are widespread cross-culturally in part because of the effects of inherent sex differences in reproductive functions on the cultural evolution of sex roles. These examples illustrate the complexity and importance of interactions between genetic and environmental factors in determining sex differences in human mortality.