Aquaporins represent a member-rich transporter protein family occurring in all kingdoms of life. Aquaporins are channel proteins that form hydrophilic pore pathways across various cellular and subcellular membranes allowing a regulated passage of diverse physiologically relevant molecules. According to functional selectivity features and substrate permeabilities, aquaporins have been designated as aqua-porins, aqua-glycero-porins, aqua-ammonia-porins, metalloido-porins, and peroxi-porins. Peroxiporins comprise those aquaporin isoforms that control hydrogen peroxide membrane permeability and therefore intercellular and interorganellar hydrogen peroxide signaling in living organisms. In this chapter, we describe the very first approaches, experiments, and discoveries, as well as the scientific settings leading to the stepwise functional identification of peroxiporins-the “how it happened”-rather than reviewing in detail the underlying datasets.