Historical and archaeological records are valuable completed experiments that shed light on how humanity has dealt with external challenges to wellness in the past. Today, we continue to face long-term challenges, such as the greenhouse effect and environmental toxicant exposure, as well as severe episodic events that include El Niño-Southern Oscillations (ENSO) and pandemics caused by emerging pathogens. This chapter considers the ways in which knowledge of our past usefully informs us today, ranging from increasing awareness about current spillover risks to directly advancing biomedical knowledge. We develop this approach as an extension of contemporary One Health concepts, termed One Paleopathology.