Suppressive anthelmintic treatment strategies originally designed to control Strongylus vulgaris in horses were extremely successful in reducing morbidity and mortality from parasitic disease. Unfortunately, this strategy has inadvertently resulted in the selection of drug-resistant cyathostomes (Cyathostominea), which are now considered the principal parasitic pathogens of horses. Resistance in the cyathostomes to benzimidazole drugs is highly prevalent throughout the world, and resistance to pyrantel appears to be increasingly common. However, there are still no reports of ivermectin resistance in nematode parasites of horses despite 20 years of use. It is unknown why resistance to ivermectin has not yet emerged, but considering that ivermectin is the single most commonly used anthelmintic in horses most parasitologists agree that resistance is inevitable. The fecal egg count reduction test is considered the gold standard for clinical diagnosis of anthelmintic resistance in horses, but diagnosis is complicated by lack of an accepted standard for the performance of this test or for the analysis and interpretation of data. Presently there is very little data available on the molecular mechanisms of anthelmintic resistance in cyathostomes; beta-tubulin gene is the only anthelmintic-resistance associated gene that has been cloned. The increasingly high prevalence of anthelmintic-resistant cyathostomes must be taken into account when designing worm control programs for horses. Strategies to decelerate further selection for drug resistance thereby extending the lifetime of currently effective anthelmintics should be implemented whenever possible. Considering the nature of the equine industry in which horses often graze shared pastures with horses from diverse locations, transmission and widespread dispersal of resistant parasites is virtually assured. A proactive approach to this problem centered on understanding the molecular basis of anthelmintic resistance in cyathostomes is required if we are to expect chemical control of nematodes in horses to remain a viable element of parasite control in the future.