Yellow fever had been around since at least the 18th century, and was known and feared throughout the 19th century, especially in port towns with the arrival of new ships. It was endemic in Cuba, so after the Spanish-American War, a Yellow Fever Commission was established in the United States to investigate. Walter Reed was the head of the commission, which established that mosquitoes transmitted the disease. The focus shifted to prevention via mosquito control.

From 1943 until her retirement in 1971, Dr. Pittman worked to assess the efficacy of and establish national and international standards for the production of the yellow fever vaccine.

After WWII, the French and 17D vaccines widely used. By 1982 the French vaccine was discontinued.  Since 1982, developments have included greater stabilization of the vaccine, with a longer storage life. In 1985, the complete genome of the yellow fever virus was published, allowing new research. Today all the vaccines are derived from two sub-strains of 17D.