Long-duration spaceflight is rapidly shifting from governmental programmes to expanding commercial ventures. Missions beyond low Earth orbit—especially lunar and Martian initiatives—pose significant physiological risks, including muscle atrophy, bone loss, neuro-ocular changes, and radiation exposure. Emerging literature discusses “biohacking” approaches such as pharmacological optimisation, somatic gene therapy, and technological augmentation to enhance resilience. Although largely experimental, these interventions may soon become relevant for private space travellers. Primary care physicians, who already manage complex decisions with limited certainty, will increasingly encounter spaceflight-related health questions.This literature review examines scientific, medical, ethical, and legal publications to identify how enhancement technologies might influence primary care practice. It assesses challenges currently discussed within astronaut health that may soon be applicable to civilian populations.A structured review of peer-reviewed biomedical, bioethical, space medicine, jurisprudence, and space-law sources was undertaken. Databases included PubMed, Scopus, HeinOnline, and Google Scholar. Search terms combined “long-duration spaceflight”, “human enhancement”, “bioethics”, “gene therapy”, “informed consent”, “space law”, and “primary care”. Inclusion criteria: publications addressing health risks of deep-space missions, enhancement strategies, ethical considerations in human research, and legal governance under international space treaties. Exclusion criteria: engineering-only documents and non-scholarly speculative material. Narrative synthesis was used.Three themes emerged. (1) Medical uncertainty: Most enhancement proposals lack long-term safety data, though the physiological pressures of deep-space missions make them scientifically appealing. (2) Ethical tension: Literature highlights risks of subtle coercion, blurred boundaries between therapy and enhancement, and challenges to meaningful informed consent in high-stakes mission environments. (3) Legal gaps: The Outer Space Treaty and related instruments contain no explicit guidance on biomedical modification of crew, creating uncertainty for clinicians and spaceflight providers.Although primary care increasingly engages with technological and ethical innovations, limited work connects astronaut health to general practice. Findings indicate that general practitioners may soon counsel patients preparing for private missions or later manage individuals who have undergone enhancement procedures.As space travel becomes accessible, primary care will face new ethical and legal considerations. Familiarity with astronaut-oriented enhancement debates will help clinicians anticipate emerging challenges. This emphasises the need for early professional awareness as human spaceflight moves closer to routine civilian experience.