Wildlife species harmful to humans are often targets of control and elimination programs. A contemporary example is the tsetse fly, a vector of sleeping sickness and African animal trypanosomosis. Tsetse flies have recently been targeted by a pan-African eradication campaign. If it is successful, the campaign could push the entire tsetse family to extinction. With the emergence of effective and efficient elimination technologies, ethical assessment of proposed elimination campaigns is urgently needed. We examine the ethics of tsetse fly elimination by considering arguments predicated on both the instrumental and the intrinsic values of the species at local and global scales. We conclude that, although global eradication of tsetse flies is not ethically justified, localized elimination campaigns targeting isolated populations are ethically defensible. We urge assessments of this kind be conducted regularly and in context, so that all relevant factors underlying decisions on species elimination are routinely laid bare for evaluation.