The moth Cactoblastis cactorum (Berg), the poster child of weed biological control in Australia, has recently invaded the United States and threatens native cacti. Concern is greatest for the endangered semaphore cactus, Opuntia corallicola, of which only two known populations exist in the wild. We made three separate outplantings of O. corallicola, designed to bolster the number of extant cacti and to test the effectiveness of three different treatments to protect the cacti from Cactoblastis. In one outplanting, we tested the associational susceptibility hypothesis and found that cacti planted more than 20 m away from the common prickly pear cactus, Opuntia stricta, which act as a reservoir of Cactoblastis, were just as frequently attacked and killed by Cactoblastis as cacti planted within 5 m. In addition, Cactoblastis attack was greater in the shade than in the sun. In the second outplanting, we minimized the attack from Cactoblastis by using protective cages planted at least 500 m from O. stricta in areas not inhabited by cacti. Cages attracted the attention of local animals, which destroyed the cages and trampled the cacti inside to death. Crown rot caused high mortality in this outplanting. In the third outplanting, again conducted at least 500 m away from O. stricta, fertilization did not reduce crown rot mortality. We suggest that increasing populations of O. corallicola in Florida, by means of outplantings, will remain a challenge because of death from Cactoblastis when planted in areas where cacti normally grow and because of death from crown rot in areas where they do not. Because Cactoblastis is moving rapidly northward and westward and has already reached Charleston, South Carolina, rare cacti in the rest of the U.S. Southeast may be in danger. Eventually, many cactus species in the U.S. South, Southwest, and Mexico will likely be threatened by this moth.