The effect of parasites on their hosts has implications for basic and applied ecology (e.g., species' population dynamics and distributions, biological control, and threats to at-risk species) and coevolution. Cuterebrid bot flies comprise one of the most-studied groups of insect parasites of mammals. Interest in their impact dates from at least 1857, when Cuterebra emasculator was so named because of the erroneous belief that its larvae castrate their hosts. This review addresses the effects of cuterebrid larvae on host biochemistry, physiology, behavior, and ecology. Despite high prevalence (peak values commonly range from 30% to 70%), at average intensities (one to three larvae per host) these parasites generally have little effect on the fitness or population dynamics of their typical hosts. This outcome likely reflects parasite/host coevolution favoring parasites that minimize harmful effects on hosts required for their survival and hosts that best tolerate perennial parasites they cannot avoid. In contrast, aggravated effects occur at higher intensities and with atypical hosts. Additional field studies involving experimental manipulation of infestation and spanning more than a few seasons are required to confirm these conclusions.