The emergence of commercial space flight means that primary care clinicians will increasingly encounter people flying into space via private providers. Unlike professional astronauts, these individuals will vary from the fit, to the unfit, to those with disorders that may, at first glance, seem disqualifying. Individuals will vary from those working in space to those embarking on space adventures. These individuals will seek medical counsel to assess their fitness to participate in space flight, the risks of doing so, and possible countermeasures to optimize the experience. Part I of this series begins with a brief summary of current knowledge of sex and gender differences in space flight, based on the experience of professional astronauts. A discussion of commercial space flight, the space context, the regulatory environment, and the basic medical examination follows. Part II then focuses on personalized precision medicine, based on integrated omics methodologies and actionable molecular analytics.