In this chapter we provide the physical and historical framework necessary to understand the emergence of Heisenberg’s 1925 paper. The aim is reconstructing the scientific context in which it took shape by describing the challenges faced by physics, and, especially, atomic physics, at the time—challenges experienced first-hand by Heisenberg himself. By highlighting the challenges, difficulties and unresolved problems of the time, we seek to shed light on the underlying motivations and needs that gave rise to Heisenberg’s work, which emerges as an attempt to address them.