Despite the long history of hormesis-related experimental research, no systematic effort to describe its early history has been undertaken. The present paper attempts to reconstruct and assess the early history of such research and to evaluate how advances in related scientific fields affected the course of hormesis-related research. The purpose of this paper is not only to satisfy this gap in current knowledge but also to provide a foundation for the assessment of how the concept of hormetic dose-response relationships may have affected the nature of the bioassay, especially with respect to hazard assessment practices within a modern risk assessment framework.