Small strongyles are highly prevalent in horses and can be found worldwide. Even though over 50 species of these parasites have been described, about 10 species comprise the bulk of the total number present in horses. Efforts to control small strongyles and other equine internal parasites have been undertaken for many years. Some of the early medications and control measures provided questionable activity against endoparasites; whether effective or not, they could be detrimental to the horse. Beginning in the early 1900s, scientific effort was used to evaluate activity of antiparasitic compounds. Only a relatively low number of classes of compounds has been used for parasite control. Progressively, in time, newer drugs have become broad-spectrum, safer, and available in lower dose rates than previously. With extensive use of parasiticides, small strongyles have been found to be resistant to all commercially-available classes of compounds except the macrocyclic lactones. Innovative parasite-control programs, relying less on drugs, need to be developed.