Invasive biological samples collected during clinical care represent a valuable yet underutilized source of information about human biology. However, the challenges of working with clinical personnel and the invasive nature of sample collection in biomedical studies can hinder the acquisition of sufficiently large sample sizes for robust statistical analyses. In addition, the incorporation of demographic data from participants is crucial for ensuring the inclusiveness of representative populations, identifying at-risk groups, and addressing healthcare disparities. Drawing on both research experiences and the existing literature, this article provides recommendations for researchers aiming to undertake efficient and impactful projects involving invasive human samples. The suggested strategies include: (1) establishing productive collaborations with clinicians; (2) optimizing sample quality through meticulous collection and handling procedures; and (3) strategically implementing a retrospective model to capitalize on existing invasive sample repositories. When established, cooperative work between clinical health care workers and biological anthropologists can yield insights into human biology that have the potential to improve human health and wellbeing.