The application of more than 91 million liters of Agent Orange in Vietnam defoliated∼ 3.1 million hectares of biologically diverse tropical forests and mangroves from Quang Tri to Ca Mau (> 1000 km) in 1961− 1971. The last application of Agent Orange in Vietnam was over for at least five decades, yet more than 4 million people, particularly local people and veterans have suffered and died from various types of cancers and congenital disabilities 1 (see also the references in Supporting Information (SI) S1). A persistent and longlasting effect component of Agent Orange is 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (2, 3, 7, 8-tetraCDD), the most toxic congener of dioxin. Dioxin and dioxin-like substances are still on the list of 10 chemicals of concern of the World Health Organization of the United Nations. 2 So far, the dioxin effects on exposed people have lasted for at least three generations. 3 The levels of dioxin in the breast milk of women 4 and serum of men 5 in sprayed regions are still several times higher than in those in nonsprayed areas, suggesting the potential effects for the next generation (s) to come. Although Agent Orange was sprayed across large areas of biodiversity hotspots and priority regions for conservation, 6 its effects on Vietnamese wildlife have been ignored in most, if not all, previous investigations. Indeed, a number of studies have documented Agent Orange effects on human health and healthcare-related issues, fewer studies on its accumulation in foods, water, sediments, and soils, and some poor documentations on the recovery of vegetation (Figure 1 and references in SI S1). Strikingly, none has tapped into the effects of Agent Orange substances on the biodiversity changes and evolutionary responses of sprayed fauna (Figure 1). This is alarming as high levels of dioxin in the soil, water, and sediments 7 could seriously affect Vietnamese wildlife animals. Recently, dioxin cleanup programs have been initiated and partly completed in several small “hotspots” of Agent Orange,