West Nile virus (WNV) causes thousands of arboviral infections in the United States each year. Patients with immune-compromising conditions and elderly people are at higher risk of severe WNV neuroinvasive disease (WNND). Despite its broad endemicity nationwide, no U.S. Food and Drug Administration-approved vaccine or therapeutic treatments exist. We summarized existing peer-reviewed literature on the preclinical development of monoclonal antibody (MAb) prophylaxis and therapeutics for the prevention and treatment of WNND. Five bibliographical databases (CINAHL, Cochrane Library, Embase, MEDLINE, and Scopus) were searched for applicable research studies performed from 1 January 1998 to 1 May 2025. In total, 2347 titles and abstracts were screened, 263 full-text publications reviewed, and 25 studies included. Studies included detailed preclinical development and evaluations of MAbs targeting the envelope (E) protein (n = 13), other viral proteins (n = 3), flaviviral cross-protective monoclonal antibodies (n = 4), and novel antibody configurations or delivery methods (n = 5). The most well-studied MAb, E16, targeting E- Domain III (E-DIII), was effective at inhibiting and treating WNND in experimental animal models. No work investigated ways to traffic therapeutic antibodies across the blood-brain barrier. This review summarizes the current research in the development of monoclonal antibody therapeutics for WNV and addresses gaps in the knowledge for future consideration.