West Nile Virus (WNV) and Usutu Virus (USUV) are neurotropic mosquito-borne viruses that primarily follow an enzootic cycle involving mosquitoes as vectors and birds as amplifying hosts. WNV was first identified in Uganda in 1937 and has since spread globally, causing periodic outbreaks of severe neuroinvasive diseases such as meningitis and encephalitis. USUV was initially isolated in 1959 in Swaziland and has also spread to Europe, primarily affecting birds with limited impact on human health. Recent expansions of these viruses' geographic range in Europe, facilitated by factors like climate change, have increased human exposure. While WNV has been more extensively studied and is a significant public health concern, USUV has gained attention due to its recent emergence in Europe and the diversity of its circulating lineages. Understanding the pathophysiology, ecology, and transmission dynamics of these viruses is crucial for effective surveillance and control measures. The article provides an overview of the current situation of WNV and USUV in Europe and outlines significant challenges that need to be addressed, including diagnostic tools, blood and organ safety, vaccines and treatments, and the development of local networks for One Health approaches.West Nile Virus (WNV) and Usutu Virus (USUV) are neurotropic mosquito-borne viruses that primarily follow an enzootic cycle involving mosquitoes as vectors and birds as amplifying hosts. WNV was first identified in Uganda in 1937 and has since spread globally, causing periodic outbreaks of severe neuroinvasive diseases such as meningitis and encephalitis. USUV was initially isolated in 1959 in Swaziland and has also spread to Europe, primarily affecting birds with limited impact on human health. Recent expansions of these viruses' geographic range in Europe, facilitated by factors like climate change, have increased human exposure. While WNV has been more extensively studied and is a significant public health concern, USUV has gained attention due to its recent emergence in Europe and the diversity of its circulating lineages. Understanding the pathophysiology, ecology, and transmission dynamics of these viruses is crucial for effective surveillance and control measures. The article provides an overview of the current situation of WNV and USUV in Europe and outlines significant challenges that need to be addressed, including diagnostic tools, blood and organ safety, vaccines and treatments, and the development of local networks for One Health approaches.