Friedrich Bonhoeffer, PhD, Corey Goodman, PhD, and Marc Tessier-Lavigne, PhD, have been pioneers in elucidating the molecular mechanisms that guide axons to their targets, a key step in the formation of neural circuits. Axon guidance was first described in the late 19th century, but the mechanisms that guide axons during brain development eluded scientists for decades. By the 1990s, axon growth was known to be guided by molecular cues, but their identity remained unknown. Bonhoeffer, Goodman, and Tessier-Lavigne were leaders in breaking through that scientific impasse. They co-discovered four major evolutionarily conserved guidance cue families – Netrins, Slits, Semaphorins and Ephrins – and many of their receptors, as well as numerous other important guidance mechanisms, transforming our understanding of how neural circuits are formed. They showed how contact attraction, chemoattraction, contact repulsion, and chemorepulsion act simultaneously and in a coordinated manner to direct axons along their paths and in forming topographic maps at their targets. Their groundbreaking findings have led to a deeper understanding of brain development and neural plasticity, with profound implications for neurodegenerative diseases such as dementia and for brain repair after injury.