The Venezuelan equine encephalitis virus (VEEV) is a major arboviral pathogen that poses a persistent public health threat, particularly through its rapid transmission among mosquitoes, birds, and horses. As the causative agent of Venezuelan equine encephalitis (VEE), VEEV belongs to the Alphavirus genus within the Togaviridae family and consists of multiple antigenic subtypes, each exhibiting distinct transmission dynamics and pathogenicity. This chapter examines the epidemiology of VEEV, focusing on the virus’s interactions with its key hosts: mosquitoes as vectors, horses as amplifying hosts, and birds as potential reservoirs. It discusses the structural and genomic characteristics of VEEV, as well as its cellular tropism and replication mechanisms, emphasizing the need for a thorough understanding of these factors to develop effective control strategies. Although VEEV infections in humans are frequently self-limiting, severe neurological complications sometimes appear in a small number of cases, including encephalitis, thereby necessitating effective diagnostic and management approaches. The chapter also explores the complex interplay between the host’s immune responses and VEEV’s immune escape, which is crucial for targeted interventions. Diagnosis requires species-specific methods such as molecular detection in mosquitoes and serological assays in horses and birds. Addressing the ongoing public health threat from VEEV demands a multifaceted strategy that includes vector control, management of reservoir populations, and the development of effective vaccines, underlining the necessity for continued interdisciplinary research and global collaboration.