In the twenty-first century, the One Health framework, which recognizes the mutual reliance of human, animal, and environmental health, has become a vital method for resolving intricate health problems. This chapter explores the historical development of One Health, from its roots in the nineteenth-century recognition of zoonotic diseases to its modern-day emphasis on transdisciplinary collaboration and systems thinking. The chapter also considers the key milestones in its development, including the contributions of early pioneers like Rudolf Virchow and Calvin Schwabe, the increasing recognition of newly arising infectious illnesses and the spread of antimicrobial resistance, along with the formal establishment of One Health programs by global entities. Furthermore, the expanding scope of One Health, encompassing not only zoonotic diseases but also food security, environmental sustainability, and social determinants of health have been discussed.