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While the first autopsy description of a brain tumour was published in the early 1600s, the first successful surgical treatment of a brain tumour did not take place until over 200 years later by William Macewen, initiating the era of modern neurosurgery. Several advancements had to take place in the late-modern era before this was possible. With the advent of anesthesia, surgeons were able to undertake more complex procedures, fostering the development of the meticulous surgical techniques that characterize the field today. Soon after, the development of aseptic technique pioneered by Joseph Lister began to combat the problem of infection which stifled surgical progress in the centuries before its introduction. Thanks to aseptic techniques, the mortality rate of surgeries showed good improvement and made it safer for patients to go under the knife. One last requirement for brain tumour surgery in an era without modern-day neuroimaging technology was the development of cerebral localization, which guided surgeons to the location of lesions in the brain and informed them of which regions were crucial for quality of life of the patient, and thus to be avoided. Therefore, with these three key developments, modern neurosurgery was able to gain a foothold with the first meningioma resection by Macewen, followed by several others in the decades to come. Progress in brain tumour surgery hit its stride in this era with Harvey Cushing and his introduction of meticulous surgical practices, his revolutionary insight into the importance of adequate intracranial pressure control, and finally the introduction of hemorrhage control through numerous techniques. Legacies of the work of early neurosurgeons can be seen in the 21st century as many of the concepts and techniques remain today, albeit moulded and refined over time.