Background: In the United States, West Nile virus (WNV) was first identified in 1999 in New York City and in Kansas in 2002. How the virus was introduced remains uncertain, although several potential methods have been hypothesized. This review presents an overview of what has occurred with WNV since 1999 and the potential for establishment of related viruses, such as Japanese encephalitis virus, if they were to be introduced in the United States.Materials and Methods: We have compiled human West Nile case data from Kansas over time with the purpose of illustrating how this virus has become endemic in the center of North America in a representative Midwestern state that is seasonal and does not have year-round mosquito vector activity. Case data were compiled from multiple sources including the U.S. Center for Disease Control and Prevention, the U.S. Department of Agriculture, and the Kansas Department of Health and Environment.Results: The annual reported numbers of human WNV infections have fluctuated widely in Kansas since the introduction in 2002. Between 2002 and 2022, there were a total of 715 reported cases in Kansas, with an average of 34 cases per year. Among the 715 cases, 73% were from 23 counties, but 4 counties accounted for 32% of this total with clusters of cases. Sedgwick County, which is the second most populous county in Kansas, represented 15% of the 715 total cases.Conclusion: The reasons for fluctuations in the number of cases reported each year and the distribution of these cases is uncertain, but they are most likely due to changes in the mosquito vector populations, which are influenced by environmental factors, such as seasonal rainfall, temperature, and humidity. With regards to the future, WNV is here to stay with annual fluctuations that are difficult to predict. The establishment of WNV in the U.S. and Kansas should serve as a warning for the possibility of establishment of other mosquito-vectored diseases, including Japanese Encephalitis virus.