Therapy with hypertonic solutions is one of the mainstays of neurosurgical treatment for all types of neurological injury. Although the initial research with hypertonic agents in the early decades of the 20th century showed great promise for these agents to lower intracranial pressure, this research also showed a considerable rate of adverse effects and complications. By the 1940s and 1950s, hypertonic therapy had been discounted as unsafe and was rarely used in neurosurgery. In the late 1950s, Manucher J. Javid and Paul Settlage at the University of Wisconsin began experimenting with infusions of urea as an agent to control intracranial pressure. Their experiments were wildly successful, and urea became a drug of major importance to neurosurgeons worldwide in only a few years. This article chronicles the work of Javid and Settlage, including a discussion of the early research on hypertonic agents, the initial difficulty the Wisconsin researchers had in disseminating their results, the widespread acceptance that followed, and the impact that these discoveries had on the neurosurgical community. The prominent place that hypertonic agents now hold in the armamentarium of neurosurgeons is owed to the work of Dr Javid, as illustrated in this historical analysis.