Rat and mouse control methods potentially affect the welfare of many millions of animals every year. Here, the humaneness of the methods used in the UK and the USA is assessed in terms of their speed and mode of action, the appearance and behaviour of affected animals, experiences of human victims, long-term effects on animals that survive exposure, and welfare risks to non-target animals. Several methods emerge as relatively humane: cyanide, alpha-chloralose, electrocution traps and well-designed snap traps all usually kill swiftly and with little distress. Preventative methods such as rodent-proofing are also humane, as well as an essential — and probably under-used — component of effective control. However, anticoagulant poisons, the most common means of controlling rodents, generally take several days to kill, during which time they cause distress, disability and/or pain. Sub-lethally affected animals are also likely to experience haemorrhages and their sequelae, and carnivores feeding on affected rodents may be secondarily poisoned. The acute rodenticides zinc phosphide and calciferol are also generally inhumane, the former typically causing severe pain for several hours, and the latter, pain and illness for several days. Sticky boards, to which rodents become adhered by the feet and fur until they are killed or simply eventually die, also raise very serious welfare concerns. This evidence highlights remarkable paradoxes in the way society treats different classes of animal, and argues for more education, legislation and research targeted at reducing the vast numbers of rodents currently killed inhumanely.