This chapter traces the history of AI from ancient myths of mechanical beings to its modern applications in drug discovery. It begins with humanity’s early fascination with thinking machines, illustrating how mythical automatons and theoretical ideas laid the groundwork for the conceptual development of AI. Moving into the scientific realm, the chapter explores the foundational advances that brought AI from theory to practice, detailing early laboratory work, initial setbacks, and the branching paths that followed. The narrative then shifts to AI’s transformative role in drug discovery, examining the milestones that have shaped its evolution in the field. Through a historical lens, this chapter highlights the challenges and breakthroughs that have driven AI’s integration into pharmaceutical research, setting the stage for the innovative approaches that continue to redefine drug discovery today.