Fire ants are stinging invasive ants from South America that infest over 129.5 million hectares in the southern United States, where eradication is no longer considered possible. The biological control of fire ants, especially by pathogens, is viewed by some as the only sustainable tactic for suppression. Microscopic-based surveys conducted in South America during the 1970s and 1980s led to the discovery of fungi and microsporidia infecting fire ants. Three of these microorganisms have been studied extensively: Beauveria bassiana 447, Thelohania solenopsae, and Vairimorpha invictae. B. bassiana 447 causes fire ant mortality but infections do not spread to queens and intercolony transmission was not evident. T. solenopsae has been found in the US and has been shown to spread naturally and debilitate colonies. Colony decline has also been associated with V. invictae, which is currently being evaluated for host specificity and possible release in the US. Through the use of molecular techniques, viruses infecting fire ant in the US have been discovered and characterized. Solenopsis invicta virus-1 can be transmitted easily to uninfected colonies and colony death often results. This virus apparently causes persistent, asymptomatic infections that actively replicate when the host is stressed. Research on fire ant-specific microsporidia and viruses, as well as other fire ant entomopathogens, is summarized to illustrate the efforts that have been undertaken to understand the biology of these pathogens and to facilitate their utilization in biological control of fire ants.