Space travel since the 1960s has led to a number of physiological alterations to homeostasis in astronauts. Extensive variation in the pattern of responses observed has led a concerted effort to develop countermeasures to overcome such changes and restore homeostasis, and thus "health" is defined as more "Earth-like". These adaptations to a space environment by a species which evolved and normally exists in the 1 g environment, the geomagnetic field, and background radiation of Earth are viewed as threats to health as defined by the conditions of Earth. Exposure to space can lead to alterations in genomic stability and epigenetic signatures, alterations which could redefine "health" and responses to risks for loss of health for those who will return to Earth. In contrast, in the future individuals born in non-Earth space environments will likely develop an integrated metabolic set point defined by those conditions. They will thus be shaped by both the local environments, and space-associated genomic/epigenomic alterations to their parents. Therefore, such an altered set point for those born and raised in non-Earth space environments will potentially have physiological and molecular consequences which may lead to either new evolutionary adaptation, or to compromise of long term health due to drastically altered set points for integrated physiologic function which is at odds with the evolutionary history of humans. The implications of the two options will be critical for defining "health" in altered environments encountered during space ventures, as well as providing insights into the regulation of human integrity at the physiological level. Therefore, the definition of "health" is dependent on the boundary conditions surrounding development and maturation, and is a dynamic concept.