Sir James Young Simpson, a Scottish physician, was no stranger to anesthesiology. In 1847, he brought ether into the realm of obstetrics but found that its odor and the large amount needed to induce unconsciousness made it impractical as an anesthetic. He therefore began a quest to find a better anesthetic, one which would cost less, would require a smaller dosage to induce unconsciousness, and would not exhibit a distinct odor. In October, 1847, a chemist named David Waldie suggested that Simpson might try chloroform as an anesthetic. Waldie was prepared to make a sample of chloroform for Simpson's evaluation purposes, but due to a fire in his own laboratory he could not do so. Simpson obtained chloroform elsewhere, and once discovered as an anesthetic, gave Waldie little credit for the original idea.

Chloroform, which had been discovered in 1831 and 1832 independently by three scientists - Samuel Guthrie, Justus von Liebig, and Eugene Soubeiran - had originally been used as a treatment for asthma. When Waldie suggested the possible anesthetic properties of chloroform to Simpson, it was only one of several chemicals already suggested to the obstetrician. In a practice of the time, Simpson invited friends to his house to try out the different chemicals on themselves. On November 4, 1847, Simpson and Drs. Matthew Duncan and George Keith, inhaled the vapors of chloroform and subsequently became unconscious. Eleven days later, a public demonstration was held at the Royal Infirmary of Edinburgh at which time chloroform's property as an anesthetic was again proven successfully. It eventually displaced ether as the anesthetic of choice throughout much of the world. Chloroform did many of the things Simpson had wanted: it's odor wasn't persistent, a lesser amount could be used to cause unconsciousness, it was cheaper, and its effects on the body occurred more rapidly than ether. Due to it's lower volatility, cost, and the amount needed for dosage, chloroform was the choice anesthetic of surgeons in the American Civil War; over a million pounds of the chemical was used in this conflict.