The United States decided to begin using chemical defoliants to decrease vegetation and deny food to the Viet Long. The use of defoliants was tested in 1961 and begun to be used in 1962. Initially every use had to be approved by President Kennedy but eventually he designated the military to decide.

The use of Herbicides became known as operation Ranch Hand. While a full range of Herbicides were used Agent Orange became the most widely known one. The use of defoliants was controversial from the start. There was questions as to whether it was legal under the Geneva Protocol Furthermore the Federation of American Scientists as well as the American Association for the Advancement of Science both criticized the use.

The operations were carried out mostly from Bien How Air Base especially for operations in the Mekong Delta. Other bases used were the Da Nang Air Base and the Phu Cat Air Base. The chemicals were sprayed from C-123 flying at low altitudes. The chemical turned out to be a carcinogen causing cancers to thousands who were involved in the program. The program continued until 1971