The science and art of neurosurgery has advanced dramatically in the past few decades, and yet its history is firmly grounded in a paradigm of surgical trial and error. Collaborations with allied specialties have made these “trials” safer, but much of what we know of functional brain anatomy comes from disease or iatrogenic perturbations. This lecture will explore the keen observations and dogged persistence that led to our current state of the art. We will explore how this surgical knowledge of the brain makes our current practice safer and how future technologies will advance our understanding with less invasive but more meaningful impact.