As commercial spaceflight expands globally, primary care physicians may increasingly be asked to assess and clear patients for space tourism or suborbital travel. The medicolegal and ethical landscape for such pre-flight evaluations remains underdeveloped, with implications for liability, informed consent, and cross-border jurisdiction. No consolidated review exists to guide primary care practice in this context.To examine existing international legal treaties, national regulations, space agency guidance, and published policy literature regarding medical screening, jurisdiction, and informed consent for commercial spaceflight participants, with particular attention to the role of primary care.A structured literature review was conducted using databases (PubMed, HeinOnline, Google Scholar) and grey literature from NASA, FAA, ESA, UN COPUOS, UK CAA, and relevant national legislation between 2004–2025. Search terms included “spaceflight participant,” “informed consent,” “aerospace medicine,” “liability,” “primary care,” and “jurisdiction.” Inclusion criteria: legal/policy/scientific publications relating to pre-flight medical screening, patient safety, and clinician responsibility. Sources were qualitatively synthesized to identify regulatory commonalities and gaps.Global legal frameworks derive from the Outer Space Treaty and Liability Convention, assigning jurisdiction to the launching state. The U.S. and U.K. require informed consent waivers disclosing the risks of unregulated human spaceflight. FAA guidelines recommend—but do not enforce—aerospace medical screening tailored to flight profiles. ESA and ISS partners define standards for “spaceflight participants” but these apply only to state-supported missions. No national regulations explicitly assign legal responsibility to primary care providers, yet doctors may face liability if screening is inadequate. Significant regulatory gaps persist in China and Japan. Across jurisdictions, consent practices, certification roles, and liability standards vary or remain undefined.The medicolegal framework for commercial spaceflight remains fragmented, and current laws focus more on operators than on clinicians. However, primary care physicians may be drawn into this evolving ecosystem through routine patient care, requiring clarity on their legal exposure, ethical duties, and referral responsibilities.Policymakers should develop international guidelines clarifying the clinical and legal responsibilities of non-specialist physicians in pre-spaceflight assessments. For now, GPs should follow aerospace medicine best practices, ensure robust informed consent, and document decisions thoroughly when approached for fitness evaluations.