The ionophores (polyether compounds) have been the predominant means of chemical control of coccidiosis in the past 15 years because of the slow development of resistant strains to them relative to other anticoccidial drugs. However, the ionophores have a narrow range of safety, and it is sometimes difficult to ensure an even distribution of the drug throughout the feed. Diagnosis of toxicity is difficult because of the reversibility of clinical signs and the variability of pathological lesions ranging from none to non-specific. This paper reviews the known pathology of ionophore toxicity and the inadequacies of present diagnostic approaches. Analysis for ionophores in feed may be made by silica gel and high performance thin layer chromatography, but tissue analyses for toxic levels, a more specific diagnostic aid, are not commonly carried out. Limited studies suggest that residues in even severely intoxicated birds remain low. Diagnosis relies upon clinical signs of incoordination, leg weakness, diarrhoea and depression, non-specific histopathological lesions of myopathy and the presence of high levels of ionophores in the feed. If, however, toxicity is due to uneven distribution, feed samples may return false negative results. Current diagnostic criteria are, therefore, unsatisfactory and there is a clear need to investigate other diagnostic approaches.