1080 (sodium fluoroacetate)-baiting programmes are an important and often the only option for reducing the impact of invasive vertebrate pests on biodiversity and agricultural production in Australia and New Zealand. These programmes are generally recognised as being target specific, and environmentally and user safe. Nevertheless, although 1080 has few recognised long-term side-effects, its potential to disrupt endocrine systems has been recently raised, and there is some conjecture regarding the humaneness of 1080 for certain target species. However, the assessment of the humaneness of any vertebrate pesticide must be commensurate with its mode of action, metabolism, target specificity, and operational use. This has not always occurred with 1080, particularly regarding these aspects, and its overall effects. The actual risk faced by non-target species during baiting operations is not accurately reflected simply by their sensitivity to 1080. 1080 is not endocrine-disrupting or carcinogenic, and because of the lag phase before signs of poisoning occur, the time from ingestion to death is not a reliable indicator of its humaneness. Moreover, functional receptors and neurological pathways are required to experience pain. However, as 1080 impairs neurological function, mainly through effects on acetylcholine and glutamate, and as this impairment includes some pain receptors, it is difficult to interpret the behaviour of affected animals, or to assess their ability to experience discomfort and pain. This has implications for assessing the merits of including ameliorative agents in 1080 baits aimed at further improving welfare outcomes. We also suggest that the assessment of the humaneness of any vertebrate pesticide should follow the ethical pest control approach, and on this basis, believe that the use of 1080 to reduce the detrimental impacts of invasive vertebrates is ethical, particularly with respect to the expectations of the wider community.