Abstract Emerging arthropod-borne viruses (arboviruses), such as chikungunya and Zika viruses, are a major threat to public health in countries like Brazil where biodiversity is high and medical care is sometimes precarious. West Nile fever is a disease caused by the West Nile Virus (WNV), an RNA virus belonging to the Flaviviridae family. It is transmitted by infected mosquitoes to numerous animals like birds, reptiles and mammals, including human and non-human primates. In the last decade, the number of reported cases of WNV infection in humans and animals has increased in the Americas. Circulation of WNV in forests and rural areas in Brazil has been detected based on serological surveys and, in 2014, the first case of West Nile fever was confirmed in a patient from Piauí State. In 2018, the virus was isolated for the first time from a horse from a rural area in the state of Espírito Santo presenting with a neurological disorder; this raises the possibility that other cases of WNV encephalitis may have occurred without clinical recognition and without laboratory diagnosis by specific assays. The imminent WNV outbreak poses a challenge for Brazilian clinicians and researchers. In this review, we summarize the basic biological and ecological characteristics of this virus and the clinical presentation and treatment of febrile illnesses caused by WNV. We also discuss the epidemiological aspects, prophylaxis of WNV infections, and monitoring strategies that could be applied in the possibility of a WNV outbreak in Brazil.