Avian influenza viruses (AIVs) have been recorded in a broad variety of hosts, including humans, terrestrial and marine mammals, and domestic and wild birds. Wild aquatic birds are recognized as the chief natural reservoirs of AIV, and their migratory flyways can serve as routes for the dispersion of the virus across countries and continents. Although AIV is one of the most studied pathogens in the world, studies on the ecology and epidemiology of this virus in South America are few and fragmented. In this review, we examine the current state of the art on the epidemiology of AIV in wild birds in South America. Current evidence corroborates that many of the broad epidemiological patterns that have been documented in other continents, such as the role played by Anseriformes and Charadriiformes in the maintenance and spread of AIV, are also true in South America. On the other hand, the fact that AIV prevalence in South American studies appears to be remarkably lower than that observed in other continents, along with the presence of endemic taxa of birds that may be highly susceptible to AIV, indicates that South America may have distinct characteristics that modulate the epidemiology of AIV in unique ways. However, our knowledge on the occurrence of AIV in South America is still limited and there are important gaps in the species and geographic distribution of the sampling effort.